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Sample records for low-density lipoprotein cholesterol

  1. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

    Science.gov (United States)

    Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

    2011-06-01

    Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

  2. Cholesterol transfer from normal and atherogenic low density lipoproteins to Mycoplasma membranes

    International Nuclear Information System (INIS)

    Mitschelen, J.J.; St Clair, R.W.; Hester, S.H.

    1981-01-01

    The purpose of this study was to determine whether the free cholesterol of hypercholesterolemic low density lipoprotein from cholesterol-fed nonhuman primates has a greater potential for surface transfer to cell membranes than does the free cholesterol of normal low density lipoprotein. The low density lipoproteins were isolated from normal and hypercholesterolemic rhesus and cynomolgus monkeys, incubated with membranes from Acholeplasma laidlawii, a mycoplasma species devoid of cholesterol in its membranes, and the mass transfer of free cholesterol determined by measuring membrane cholesterol content. Since these membranes neither synthesize nor esterify cholesterol, nor degrade the protein or cholesterol ester moieties of low density lipoprotein, they are an ideal model with which to study differences in the cholesterol transfer potential of low density lipoprotein independent of the uptake of the intact low density lipoprotein particle. These studies indicate that, even though there are marked differences in the cholesterol composition of normal and hypercholesterolemic low density lipoproteins, this does not result in a greater chemical potential for surface transfer of free cholesterol. Consequently, if a difference in the surface transfer of free cholesterol is responsible for the enhanced ability of hypercholesterolemic low density lipoprotein to promote cellular cholesterol accumulation and, perhaps, also atherosclerosis, it must be the result of differences in the interaction to the hypercholesterolemic low density lipoprotein with the more complicated mammalian cell membranes, rather than differences in the chemical potential for cholesterol transfer

  3. Neutrophil–lymphocyte ratio is associated with low high-density lipoprotein cholesterol in healthy young men

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    Duran Tok

    2014-04-01

    Full Text Available Objective: It has been reported that the neutrophil–lymphocyte ratio is significantly elevated in patients with low high-density lipoprotein cholesterol (<35 mg/dL. But in this study, some patients had hypertension that may have affected the neutrophil–lymphocyte ratio. This study consisted of 1274 asymptomatic healthy young men. In contrast with the previous study, we investigated the neutrophil–lymphocyte ratio in healthy young men with low high-density lipoprotein cholesterol compared with controls. Methods: We studied 1274 asymptomatic young males (military personnel screening who underwent routine health check-up. Of them, 102 subjects had low high-density lipoprotein cholesterol. Results: The neutrophil–lymphocyte ratio was significantly higher among the men with low high-density lipoprotein cholesterol than that of the control group (P < 0.001. Conclusion: We conclude that the neutrophil–lymphocyte ratio is significantly elevated in asymptomatic healthy young men with low high-density lipoprotein cholesterol compared with control participants.

  4. Nonfasting Triglycerides, Low-Density Lipoprotein Cholesterol, and Heart Failure Risk

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2018-01-01

    OBJECTIVE: The prevalence of heart failure is increasing in the aging population, and heart failure is a disease with large morbidity and mortality. There is, therefore, a need for identifying modifiable risk factors for prevention. We tested the hypothesis that high concentrations of nonfasting...... triglycerides and low-density lipoprotein cholesterol are associated with higher risk of heart failure in the general population. APPROACH AND RESULTS: We included 103 860 individuals from the Copenhagen General Population Study and 9694 from the Copenhagen City Heart Study in 2 prospective observational...... association studies. Nonfasting triglycerides and low-density lipoprotein cholesterol were measured at baseline. Individuals were followed for ≤23 years, during which time 3593 were diagnosed with heart failure. Hazard ratios were estimated using Cox proportional hazard regression models. In the Copenhagen...

  5. Low-density lipoprotein cholesterol and risk of gallstone disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  6. Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

    Science.gov (United States)

    Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

    2015-02-13

    Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

  7. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey

    2015-01-01

    RATIONALE: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because...

  8. Comparison of different statin therapy to change low-density lipoprotein cholesterol and high-density lipoprotein cholesterol level in Korean patients with and without diabetes.

    Science.gov (United States)

    Khang, Ah Reum; Song, Young Shin; Kim, Kyoung Min; Moon, Jae Hoon; Lim, Soo; Park, Kyong Soo; Jang, Hak Chul; Choi, Sung Hee

    2016-01-01

    It is difficult to apply the proper intensity of statin for new treatment guidelines in clinical settings because of few data about the statin efficacy in Asians. We conducted a retrospective, observational study to estimate the percentage changes in lipid parameters and glucose induced by different statins. We analyzed 3854 patients including those with nondiabetes and diabetes treated at the outpatient clinic between 2003 and 2013 who were statin-naïve and maintained fixed-dose of statin for at least 18 months. Moderate- and low-intensity statin therapy was effective in reducing low-density lipoprotein cholesterol (LDL-C) to statin group. The effects of statins in elevating high-density lipoprotein cholesterol were similar in each statin groups, except the ezetimibe-simvastatin group (4.5 ± 2.1%) and high-dose atorvastatin groups (9.7 ± 3.3% and 8.7 ± 2.4% for 40 mg and 80 mg of atorvastatin/day, respectively). High-density lipoprotein cholesterol increased less and LDL-C decreased more in diabetes than in nondiabetes. There were no significant changes of fasting glucose after statin use in nondiabetic patients. Moderate- or low-intensity statin was effective enough in reaching National Cholesterol Education Program Adult Treatment Panel III LDL-C target goals in Koreans. Low-intensity statin showed around 30% LDL-C reduction from the baseline level in Koreans, which is comparable to moderate-intensity statin in new guideline. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  9. Elevated plasma low-density lipoprotein and high-density lipoprotein cholesterol levels in amenorrheic athletes: effects of endogenous hormone status and nutrient intake.

    Science.gov (United States)

    Friday, K E; Drinkwater, B L; Bruemmer, B; Chesnut, C; Chait, A

    1993-12-01

    To determine the interactive effects of hormones, exercise, and diet on plasma lipids and lipoproteins, serum estrogen and progesterone levels, nutrient intake, and plasma lipid, lipoprotein, and apolipoprotein concentrations were measured in 24 hypoestrogenic amenorrheic and 44 eumenorrheic female athletes. When compared to eumenorrheic athletes, amenorrheic athletes had higher levels of plasma cholesterol (5.47 +/- 0.17 vs. 4.84 +/- 0.12 mmol/L, P = 0.003), triglyceride (0.75 +/- 0.06 vs. 0.61 +/- 0.03 mmol/L, P = 0.046), low-density lipoprotein (LDL; 3.16 +/- 0.15 vs. 2.81 +/- 0.09 mmol/L, P = 0.037), high-density lipoprotein (HDL; 1.95 +/- 0.07 vs. 1.73 +/- 0.05 mmol/L, P = 0.007), and HDL2 (0.84 +/- 0.06 vs. 0.68 +/- 0.04 mmol/L, P = 0.02) cholesterol. Plasma LDL/HDL cholesterol ratios, very low-density lipoprotein and HDL3 cholesterol, and apolipoprotein A-I and A-II levels were similar in the two groups. Amenorrheic athletes consumed less fat than eumenorrheic subjects (52 +/- 5 vs. 75 +/- 3 g/day, P = 0.02), but similar amounts of calories, cholesterol, protein, carbohydrate, and ethanol. HDL cholesterol levels in amenorrheic subjects correlated positively with the percent of dietary calories from fat (r = 0.42, n = 23, P = 0.045) but negatively with the percent from protein (r = -0.49, n = 23, P = 0.017). Thus, exercise-induced amenorrhea may adversely affect cardiovascular risk by increasing plasma LDL and total cholesterol. However, cardioprotective elevations in plasma HDL and HDL2 cholesterol may neutralize the risk of cardiovascular disease in amenorrheic athletes.

  10. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  11. Changes in plasma low-density lipoprotein (LDL)- and high-density lipoprotein cholesterol in hypo- and hyperthyroid patients are related to changes in free thyroxine, not to polymorphisms in LDL receptor or cholesterol ester transfer protein genes

    NARCIS (Netherlands)

    Diekman, M. J.; Anghelescu, N.; Endert, E.; Bakker, O.; Wiersinga, W. M.

    2000-01-01

    Thyroid function disorders lead to changes in lipoprotein metabolism. Both plasma low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increase in hypothyroidism and decrease in hyperthyroidism. Changes in LDL-C relate to altered clearance of LDL particles

  12. Metabolism of cholesteryl esters of rat very low density lipoproteins.

    Science.gov (United States)

    Faergeman, O; Havel, R J

    1975-06-01

    Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent.

  13. Comparison of soymilk and probiotic soymilk effects on serum high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in diabetic Wistar rats

    Directory of Open Access Journals (Sweden)

    Mina Babashahi

    2015-04-01

    Full Text Available BACKGROUND: Soy milk (SM and its fermented products are identified as rich sources of bioactive compounds helping to manage and to reduce the risk of chronic disease. This study aimed to compare the effects of SM and probiotic SM (PSM consumption on serum low-density lipoprotein cholesterol (LDL-C and high-density lipoprotein cholesterol (HDL-C in diabetic Wistar rats. METHODS: Probiotic SM was prepared by fermentation of the plain SM with a native strain of Lactobacillus plantarum. 20 streptozotocin-nicotinamide-induced diabetic Wistar rats were divided into two groups based on the type of administered SM (SM group and PSM group. The animals were fed with 1 ml/day of either soy or PSM for 21 days. The serum lipoprotein levels were analyzed at baseline and the end of the intervention period. RESULTS: HDL-C increased significantly in PSM group. Furthermore, this group showed more percent of change in increased HDL-C in compression with SM group (P < 0.050. Regarding LDL-C level, rats fed with SM was not significantly different from the PSM group (P < 0.050; though, this biomarker was reduced in both group. CONCLUSION: Probiotic SM could modulate blood lipoprotein levels. Thus, it may be considered in managing diabetes complications and atherosclerotic risks. 

  14. Effects of maximal doses of atorvastatin versus rosuvastatin on small dense low-density lipoprotein cholesterol levels

    Science.gov (United States)

    Maximal doses of atorvastatin and rosuvastatin are highly effective in lowering low-density lipoprotein (LDL) cholesterol and triglyceride levels; however, rosuvastatin has been shown to be significantly more effective than atorvastatin in lowering LDL cholesterol and in increasing high-density lipo...

  15. Comparison of human plasma low- and high-density lipoproteins as substrates for lecithin: cholesterol acyltransferase.

    Science.gov (United States)

    Barter, P J; Hopkins, G J; Gorjatschko, L

    1984-01-17

    A recent observation that lecithin: cholesterol acyltransferase (EC 2.3.1.43) interacts with both low-density lipoproteins (LDL) and high-density lipoproteins (HDL) in human plasma is in apparent conflict with an earlier finding that the purified enzyme, while highly reactive with isolated HDL, was only minimally reactive with LDL. There is evidence, however, that lecithin: cholesterol acyltransferase may exist physiologically as a component of a complex with other proteins and that studies with the isolated enzyme may therefore provide misleading results. Consequently, interactions of the enzyme with isolated human lipoproteins have been re-examined in incubations containing lecithin: cholesterol acyltransferase as a component of human lipoprotein-free plasma in which a physiologically active complex of the enzyme with other proteins may have been preserved. In this system there was a ready esterification of the free cholesterol associated with both LDL and HDL-subfraction 3 (HDL3) in reactions that obeyed typical enzyme-saturation kinetics. For a given preparation of lipoprotein-free plasma the Vmax values with LDL and with HDL3 were virtually identical. The apparent Km for free cholesterol associated with HDL3 was 5.6 X 10(-5) M, while for that associated with LDL it was 4.1 X 10(-4) M. This implied that, in terms of free cholesterol concentration, the affinity of HDL3 for lecithin: cholesterol acyltransferase was about 7-times greater than that of LDL. When expressed in terms of lipoprotein particle concentration, however, it was apparent that the affinity of LDL for the enzyme was considerably greater than that of HDL3. When the lipoprotein fractions were equated in terms of lipoprotein surface area, the apparent affinities of the two fractions for the enzyme were found to be comparable.

  16. Anthocyanins increase low-density lipoprotein and plasma cholesterol and do not reduce atherosclerosis in Watanabe Heritable Hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Nielsen, I. L. F.; Rasmussen, S.E.; Mortensen, Alicja

    2005-01-01

    a purified anthocyanin fraction front black currants, a black currant juice, probucol or control diet for 16 weeks. Purified anthocyanins significantly increased plasma cholesterol and low-density lipoprotein (LDL) cholesterol. Intake of black currant juice had no effect on total plasma cholesterol......, but lowered very-low-density lipoprotein (VLDL) cholesterol significantly. There were no significant effects of either purified anthocyanins or black currant juice on aortic cholesterol or development of atherosclerosis after 16 weeks. Probucol had no effect on plasma cholesterol but significantly lowered......, antioxidant enzymes, protein and lipid oxidation were not affected by any of the anthocyanin treatments. Adverse effects of purified anthocyanins were observed on plasma- and LDL-cholesterol. These effects were not observed with black currant juice, suggesting that black currants may contain components...

  17. Genetics, Lifestyle, and Low-Density Lipoprotein Cholesterol in Young and Apparently Healthy Women

    NARCIS (Netherlands)

    Balder, Jan-Willem; Rimbert, Antoine; Zhang, Xiang; Viel, Martijn; Kanninga, Roan; van Dijk, Freerk; Lansberg, Peter; Sinke, Richard; Kuivenhoven, Jan Albert

    2018-01-01

    BACKGROUND: Atherosclerosis starts in childhood but low-density lipoprotein cholesterol (LDL-C), a causal risk factor, is mostly studied and dealt with when clinical events have occurred. Women are usually affected later in life than men and are underdiagnosed, undertreated, and understudied in

  18. Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?

    NARCIS (Netherlands)

    Rana, Jamal S.; Boekholdt, S. Matthijs

    2010-01-01

    Purpose of review Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the

  19. Alterations of serum cholesterol and serum lipoprotein in breast cancer of women

    OpenAIRE

    Hasija, Kiran; Bagga, Hardeep K.

    2005-01-01

    Fasting blood sample of 50 normal subjects (control) and 100 patients of breast cancer were investigated for serum total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, very low density lipoprotein, high density lipoprotein cholesterol:low density lipoprotein cholesterol ratio and total cholesterol:high density lipoprotein cholesterol ratio during breast cancer of women. Five cancer stages, types, age groups, parity and menopausal status were undertaken...

  20. Treating patients with low high-density lipoprotein cholesterol: choices, issues and opportunities

    Directory of Open Access Journals (Sweden)

    Watts Gerald F

    2001-05-01

    Full Text Available Abstract Three clinical trials have recently focused on the benefits of lipid-regulating therapy in populations with normocholesterolaemia and low high-density lipoprotein (HDL-cholesterol. Two secondary prevention studies (Veterans Affairs HDL-Cholesterol Intervention Trial [VA-HIT] and Bezafibrate Infarction Prevention [BIP] trial testified to the efficacy of fibrates in decreasing cardiovascular events, particularly in patients with coexisting risk factors, including hypertriglyceridaemia. The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS demonstrated that a statin could decrease acute coronary events in patients with isolated low HDL-cholesterol in a primary prevention setting. The absolute risk reduction in coronary events in the VA-HIT study compares favourably with those reported from the statin-based Cholesterol and Recurrent Events (CARE and Long-term Intervention with Pravastatin in Ischaemic Disease (LIPID trials. The absolute risk reduction in AFCAPS-TexCAPS is similar to that in West of Scotland Coronary Pravastatin Study (WOSCOPS. Recommendations are given concerning lifestyle and pharmacological management of low HDL-cholesterol. Optimal management also requires review of current treatment targets for HDL-cholesterol and triglycerides levels.

  1. High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C

    NARCIS (Netherlands)

    Bochem, Andrea E.; Holleboom, Adriaan G.; Romijn, Johannes A.; Hoekstra, Menno; Dallinga-Thie, Geesje M.; Motazacker, Mahdi M.; Hovingh, G. Kees; Kuivenhoven, Jan A.; Stroes, Erik S. G.

    2013-01-01

    Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To

  2. Relationship between low-density lipoprotein cholesterol and severe acute pancreatitis (“the lipid paradox”

    Directory of Open Access Journals (Sweden)

    Hong W

    2018-05-01

    Full Text Available Wandong Hong,1,* Vincent Zimmer,2,3,* Simon Stock,4,* Maddalena Zippi,5 Jones AQ Omoshoro-Jones,6 Mengtao Zhou71Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Medicine II, Saarland University Medical Center, Saarland University, Homburg, Germany; 3Department of Medicine, Marienhausklinik St Josef Kohlhof, Neunkirchen, Germany; 4Department of Surgery, World Mate Emergency Hospital, Battambang, Cambodia; 5Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome, Italy; 6Department of Surgery, Chris Hani-Baragwanath Academic Hospital, University of the Witwatersrand, Johannesburg, South Africa; 7Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China*These authors contributed equally to this workBackground and aim: The aim of this study was to investigate the association between low-density lipoprotein cholesterol (LDL-C and the development of severe acute pancreatitis (SAP.Patients and methods: A total of 674 patients with acute pancreatitis were enrolled. Nonlinearity in the relationship between LDL-C and SAP was assessed by restricted cubic spline analysis. Univariable and multivariable regression analyses were used to identify independent risk factors of SAP.Results: The restricted cubic spline analysis suggested a nonlinear association between high-density lipoprotein cholesterol (HDL-C, LDL-C and triglyceride levels and incidence of SAP. The incidence of SAP in patients with low LDL-C (<90 mg/dL, moderate LDL-C (90–150 mg/dL and high LDL-C (>150 mg/dL levels was 15.1%, 3.7% and 9.8%, respectively. Multivariable analysis confirmed that low LDL-C levels (odds ratio [OR] 3.05; 95% confidence interval [CI] 1.35–6.90, high LDL-C levels (OR 4.42; 95% CI 1.41–13.87 and low HDL-C levels (OR 6.90; 95% CI 2.61–18.23 but

  3. Glycated albumin and direct low density lipoprotein cholesterol levels in type 2 diabetes mellitus

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  4. Prevalence of Low High-density Lipoprotein Cholesterol Among Adults, by Physical Activity: United States, 2011-2014.

    Science.gov (United States)

    Zwald, Marissa L; Akinbami, Lara J; Fakhouri, Tala H I; Fryar, Chryl D

    2017-03-01

    Data from the National Health and Nutrition Examination Survey •The prevalence of low high-density lipoprotein (HDL) cholesterol was significantly higher among adults who did not meet recommended physical activity guidelines (21.0%) than adults who met the guidelines (17.7%). •Low HDL cholesterol prevalence differed significantly for both men and women by adherence to physical activity guidelines. •Prevalence of low HDL cholesterol declined as age increased for both those who did and did not meet the physical activity guidelines. •Non-Hispanic white and non-Hispanic black adults who did not meet the physical activity guidelines had a higher prevalence than those who met the guidelines. •Low HDL cholesterol prevalence declined with increasing education level regardless of adherence to physical activity guidelines. Regular physical activity can improve cholesterol levels among adults, including increasing high-density lipoprotein (HDL) cholesterol (1). HDL cholesterol is known as "good" cholesterol because high levels can reduce cardiovascular disease risk (2). The 2008 Physical Activity Guidelines for Americans recommend that adults engage in 150 minutes or more of moderate-intensity aerobic activity per week, 75 minutes of vigorous-intensity aerobic activity per week, or an equivalent combination (3). Adherence to these guidelines is expected to decrease the prevalence of low HDL cholesterol levels (4-8). This report presents national data for 2011-2014 on low HDL cholesterol prevalence among U.S. adults aged 20 and over, by whether they met these guidelines. All material appearing in this report is in the public domain and may be reproduced or copied without permission; citation as to source, however, is appreciated.

  5. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high......-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic...

  6. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  7. Low-density lipoprotein analysis in microchip capillary electrophoresis systems

    NARCIS (Netherlands)

    Ceriotti, Laura; Shibata, Takayuki; Folmer, Britta; Weiller, Bruce H.; Roberts, Matthew A.; De Rooij, Nico F.; Verpoorte, Elisabeth

    2002-01-01

    Due to the mounting evidence for altered lipoprotein and cholesterol-lipoprotein content in several disease states, there has been an increasing interest in analytical methods for lipoprotein profiling for diagnosis. The separation of low- and high-density lipoproteins (LDL and HDL, respectively)

  8. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    NARCIS (Netherlands)

    Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density

  9. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    DEFF Research Database (Denmark)

    Chapman, M John; Ginsberg, Henry N; Amarenco, Pierre

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipop...

  10. Identifying low density lipoprotein cholesterol associated variants in the Annexin A2 (ANXA2) gene

    DEFF Research Database (Denmark)

    Fairoozy, Roaa Hani; Cooper, Jackie; White, Jon

    2017-01-01

    Background and aims: Annexin-A2 (AnxA2) is an endogenous inhibitor of proprotein convertase subtilisin/kexin type-9 (PCSK9). The repeat-one (R1) domain of AnxA2 binds to PCSK9, blocking its ability to promote degradation of low-density lipoprotein cholesterol-receptors (LDL-R) and thereby regulat...

  11. [THE SPIRIT CHOLESTEROL, BIOLOGICA L ROLE AT STAGES OF PHYLOGENESIS, MECHANISMS OF INHIBITION OF SYNTHESIS OF STEROL BY STATINS, FACTORS OF PHARMACOGENOMICS AND DIAGNOSTIC SIGNIFICANCE OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    Science.gov (United States)

    Titov, V N; Kotlovskii, M Yu; Pokrovskii, A A; Kotlovskaia, O S; Osedko, A V; Titova, N M; Kotlovskii, Yu V; Digaii, A M

    2015-04-01

    The hypolipidemic effect of statins is realized by inhibition of synthesis of local pool of cholesterol spirit in endoplasmic net of hepatocytes. The cholesterol spirit covers all hydrophobic medium of triglycerides with polar mono layer of phosphatidylcholines and cholesterol spirit prior to secretion of lipoproteins of very low density into hydrophilic medium. The lesser mono layer between lipase enzyme and triglycerides substrate contains of cholesterol spirit the higher are the parameters of hydrolysis of palmitic and oleic lipoproteins of very low density. The sequence of effect of statins is as follows: blocking of synthesis in hepatocytes and decreasing of content of unesterified cholesterol spirit in blood plasma; activation of hydrolysis of triglycerides in palmitic and oleic lipoproteins of very low density; formation of ligand lipoproteins of very low density and their absorption by cells by force of apoB-100 endocytosis; decreasing in blood of content of polyenoic fatty acids, equimolar esterified by cholesterol spirit, polyethers of cholesterol spirit and decreasing of level of cholesterol spirit-lipoproteins of very low density. There is no way to eliminate aphysiological effect of disordered biological function of trophology (nutrition) on metabolism of fatty acids in population by means of pharmaceuticals intake. It is necessary to eliminate aphysiological effect of environment. To decrease rate of diseases of cardiovascular system one has to decrease in food content of saturated fatty acids and in the first instance palmitic saturated fatty acid, trans-form fatty acid, palmitoleic fatty acids up to physiological values and increase to the same degree the content of polyenoic fatty acids. The saturated fatty acids block absorption of polyenoic fatty acids by cells. The atherosclerosis is a deficiency of polyenoic fatty acids under surplus of palmitic saturated fatty acid.

  12. Gemfibrozil treatment of the high triglyceride-low high-density lipoprotein cholesterol trait in men with established atherosclerosis

    NARCIS (Netherlands)

    Knipscheer, H. C.; Nurmohamed, M. T.; van den Ende, A.; Plaat, B.; Pruijs, H. J.; Mulder, W. J.; Kastelein, J. J.

    1994-01-01

    To study the short-term efficacy, tolerability and safety of the treatment with gemfibrozil 600 mg twice daily or placebo in male patients with established atherosclerosis, with a lipid profile matching the 'high triglyceride-low high-density lipoprotein (HDL) cholesterol trait'. Double-blind

  13. The levels of plasma low density lipoprotein are independent of cholesterol ester transfer protein in fish-oil fed F1B hamsters

    Directory of Open Access Journals (Sweden)

    Davis Phillip J

    2005-03-01

    Full Text Available Abstract Background Cholesterol ester transfer protein (CETP plays a major role in regulating the levels of LDL- and HDL-cholesterol. We previously observed a fish-oil-induced elevation of low-density lipoprotein (LDL-and very-low-density lipoprotein (VLDL-cholesterol concentrations and a decrease in high-density lipoprotein (HDL-cholesterol concentration in F1B hamsters. The molecular mechanism/s by which fish oil induces hyperlipidaemic effect was investigated in this study. We examined whether the effects of dietary fish oil on plasma lipoprotein concentrations are due to fish-oil-induced alterations in plasma CETP activity. MIX diet, a diet supplemented with a mixture of lard and safflower oil, was used as the control diet. Results We found that fish oil feeding in hamsters reduced CETP mass as well as CETP activity. Increasing the dietary fat level of fish-oil from 5% to 20% (w/w led to a further decrease in CETP mass. Supplementation with dietary cholesterol increased both CETP mass and CETP activity in fish-oil and MIX-diet fed hamsters. However, there was no correlation between CETP mass as well as CETP activity and LDL-cholesterol concentrations. Conclusion These findings suggest that cholesterol ester transfer between HDL and LDL is not likely to play a major role in determining fish-oil-induced changes in LDL- and HDL-cholesterol concentrations in F1B hamsters. A possible role of reduced clearance of LDL-particles as well as dietary fat level and dietary cholesterol dependent changes in LDL-lipid composition have been discussed.

  14. Role of low density lipoprotein-bound cholesterol esters in acute lymphoblastic leukemia cells

    International Nuclear Information System (INIS)

    Cutts, J.L.; Madden, E.A.; Melnykovych, G.

    1986-01-01

    The glucocorticoid sensitive CEM-C7 T-cell line was derived from human acute lymphoblastic leukemia cells by Norman and Thompson. Madden et al. have demonstrated that this growth inhibitory effect is due in part to a glucocorticoid-mediated inhibition of cholesterol synthesis and can be partially reversed by cholesterol dispersions. To further delineate the role of cholesterol in this growth inhibition, they have examined the ability of low density lipoprotein (LDL)-bound [ 3 H]cholesterol linoleate to reverse the growth inhibitory effect of 1 μM dexamethasone (Dex) on the CEM-C7 cells. LDL-bound cholesterol linoleate was unable to reverse the Dex-mediated growth inhibition, although incorporation of [ 14 C] acetate into free cholesterol was inhibited by 29%, following the Brown and Goldstein model. The presence of Dex further inhibited acetate incorporation into free cholesterol in the LDL-treated cells. Under all conditions, more than 99% of the acetate incorporated into cholesterol was present as free cholesterol, while over 87% of the LDL-bound cholesterol linoleate taken up remained in the ester compartment. These results indicate that CEM-C7 cells are unable to utilize LDL-bound cholesterol esters as a source of free cholesterol and rely on endogenous synthesis for their free cholesterol requirements

  15. Current guidelines for high-density lipoprotein cholesterol in therapy and future directions

    Directory of Open Access Journals (Sweden)

    Subedi BH

    2014-04-01

    Full Text Available Bishnu H Subedi,1,2 Parag H Joshi,1 Steven R Jones,1 Seth S Martin,1 Michael J Blaha,1 Erin D Michos1 1Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, 2Greater Baltimore Medical Center, Baltimore, MD, USA Abstract: Many studies have suggested that a significant risk factor for atherosclerotic cardiovascular disease (ASCVD is low high-density lipoprotein cholesterol (HDL-C. Therefore, increasing HDL-C with therapeutic agents has been considered an attractive strategy. In the prestatin era, fibrates and niacin monotherapy, which cause modest increases in HDL-C, reduced ASCVD events. Since their introduction, statins have become the cornerstone of lipoprotein therapy, the benefits of which are primarily attributed to decrease in low-density lipoprotein cholesterol. Findings from several randomized trials involving niacin or cholesteryl ester transfer protein inhibitors have challenged the concept that a quantitative elevation of plasma HDL-C will uniformly translate into ASCVD benefits. Consequently, the HDL, or more correctly, HDL-C hypothesis has become more controversial. There are no clear guidelines thus far for targeting HDL-C or HDL due to lack of solid outcomes data for HDL specific therapies. HDL-C levels are only one marker of HDL out of its several structural or functional properties. Novel approaches are ongoing in developing and assessing agents that closely mimic the structure of natural HDL or replicate its various functions, for example, reverse cholesterol transport, vasodilation, anti-inflammation, or inhibition of platelet aggregation. Potential new approaches like HDL infusions, delipidated HDL, liver X receptor agonists, Apo A-I upregulators, Apo A mimetics, and gene therapy are in early phase trials. This review will outline current therapies and describe future directions for HDL therapeutics. Keywords: high-density lipoprotein, lipids, cholesterol, atherosclerosis, cardiovascular disease, therapy

  16. Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data.

    Directory of Open Access Journals (Sweden)

    Simon C Mathews

    Full Text Available BACKGROUND: Epidemiologic studies suggest that LDL particle concentration (LDL-P may remain elevated at guideline recommended LDL cholesterol goals, representing a source of residual risk. We examined the following seven separate lipid parameters in achieving the LDL-P goal of <1000 nmol/L goal for very high risk secondary prevention: total cholesterol to HDL cholesterol ratio, TC/HDL, <3; a composite of ATP-III very high risk targets, LDL-C<70 mg/dL, non-HDL-C<100 mg/dL and TG<150 mg/dL; a composite of standard secondary risk targets, LDL-C<100, non-HDL-C<130, TG<150; LDL phenotype; HDL-C ≥ 40; TG<150; and TG/HDL-C<3. METHODS: We measured ApoB, ApoAI, ultracentrifugation lipoprotein cholesterol and NMR lipoprotein particle concentration in 148 unselected primary and secondary prevention patients. RESULTS: TC/HDL-C<3 effectively discriminated subjects by LDL-P goal (F = 84.1, p<10(-6. The ATP-III very high risk composite target (LDL-C<70, nonHDL-C<100, TG<150 was also effective (F = 42.8, p<10(-5. However, the standard secondary prevention composite (LDL-C<100, non-HDL-C<130, TG<150 was also effective but yielded higher LDL-P than the very high risk composite (F = 42.0, p<10(-5 with upper 95% confidence interval of LDL-P less than 1000 nmol/L. TG<150 and TG/HDL-C<3 cutpoints both significantly discriminated subjects but the LDL-P upper 95% confidence intervals fell above goal of 1000 nmol/L (F = 15.8, p = 0.0001 and F = 9.7, p = 0.002 respectively. LDL density phenotype neared significance (F = 2.85, p = 0.094 and the HDL-C cutpoint of 40 mg/dL did not discriminate (F = 0.53, p = 0.47 alone or add discriminatory power to ATP-III targets. CONCLUSIONS: A simple composite of ATP-III very high risk lipoprotein cholesterol based treatment targets or TC/HDL-C ratio <3 most effectively identified subjects meeting the secondary prevention target level of LDL-P<1000 nmol/L, providing a potential alternative to advanced lipid testing in many clinical

  17. Early incorporation of cell-derived cholesterol into pre-beta-migrating high-density lipoprotein

    International Nuclear Information System (INIS)

    Castro, G.R.; Fielding, C.J.

    1988-01-01

    Cultures of human skin fibroblasts were labeled to high cholesterol specific activity with [ 3 H]cholesterol and incubated briefly (1-3 min) with normal human plasma. The plasma was fractionated by two-dimensional agarose-polyacrylamide gel electrophoresis and the early appearance of cholesterol label among plasma lipoproteins determined. A major part of the label at 1-min incubation was in a pre-beta-migrating apo A-I lipoprotein fraction with a molecular weight of ca. 70,000. Label was enriched about 30-fold in this fraction relative to its content of apo A-I (1-2% of total apo A-I). The proportion of label in this lipoprotein was strongly correlated with its concentration in plasma. Further incubation (2 min) in the presence of unlabeled cells demonstrated transfer of label from this fraction to a higher molecular weight pre-beta apo A-I species, to low-density lipoprotein, and to the alpha-migrating apo A-I that made up the bulk (96%) of total apo A-I in plasma. The data suggest that a significant part of cell-derived cholesterol is transferred specifically to a pre-beta-migrating lipoprotein A-I species as part of a cholesterol transport transfer sequence in plasma

  18. Increased oxidizability of low-density lipoproteins in hypothyroidism

    NARCIS (Netherlands)

    Diekman, T.; Demacker, P. N.; Kastelein, J. J.; Stalenhoef, A. F.; Wiersinga, W. M.

    1998-01-01

    Hypothyroidism leads to an increase of plasma low-density lipoprotein (LDL) cholesterol levels. Oxidation of LDL particles changes their intrinsic properties, thereby enhancing the development of atherosclerosis. T4 has three specific binding sites on apolipoprotein B; furthermore it inhibits LDL

  19. Low-density lipoprotein cholesterol is associated with fracture risk in diabetes patients - a nested case-control study

    DEFF Research Database (Denmark)

    Starup-Linde, Jakob; Gregersen, Søren; Vestergaard, Peter

    2014-01-01

    available for an analysis of patient characteristics, co-morbidities, biochemical parameters and drug usage. Results: Patient age at the time of diabetes diagnosis, a diagnosis of previous fracture, an alcohol related diagnosis, total cholesterol level, and the usage of antidepressants, antiepileptics...... and insulin all increased the odds of fracture. Low-density lipoprotein cholesterol (LDL) levels decreased the odds of fracture, where the level of 3.04-5.96 mmol/l was optimal with regard to fracture risk. Conclusion: LDL may add to the understanding of fractures in diabetes patients and it may be added...

  20. Serum oxidized low density lipoprotein levels in preeclamptic and normotensive pregnants.

    Science.gov (United States)

    Kozan, A; Yildirmak, S Turkmen; Mihmanli, V; Ayabakan, H; Cicek, Y G; Kalaslioglu, V; Doean, S; Cebeci, H Cerci

    2015-01-01

    BACKGROUNDS/AIM: The aim of the study was to determine serum lipids and oxidized low density lipoprotein (ox-LDL) levels in preeclamptic pregnants and compare with those of normotensives. Ox-LDL levels were determined by enzyme linked immunosorbent assay (ELISA); total cholesterol, hight density lipoprotein (HDL)-cholesterol and triglyceride levels were measured by enzymatic colorimetric assay in 26 normotensive and 27 preeclamptic pregnants. LDL and very low density lipoprotein (VLDL) cholesterol was calculated by Friedwald formula. Serum levels of Ox-LDL (U/L), total-cholesterol (mg/dL), HDL-cholesterol (mg/dL), LDL-cholesterol (mg/dL), triglyceride (mg/dL), and VLDL-cholesterol (mg/dL) in normotensive and preeclamptic pregnants were found as 130±60 and 133±69; 248±49 and 248±81; 67±14 and 61±16; 147±61 and 135±59; 207±76 and 256±87; 41±15 and 50±17, respectively. Mean values of Ox-LDL and other lipid parameters were higher than the upper limits of their reference ranges in both of groups. However no significant differences were found in Ox-LDL, total, HDL and LDL-cholesterol levels between two groups. However, the levels of triglyceride and VLDL-cholesterol were significantly higher in preeclampsia group. The present results suggest that the levels of serum Ox-LDL and other lipid parameters rise as a result of pregnancy rather than as a result of preeclampsia.

  1. High-density lipoprotein cholesterol: How High

    Directory of Open Access Journals (Sweden)

    G Rajagopal

    2012-01-01

    Full Text Available The high-density lipoprotein cholesterol (HDL-C is considered anti-atherogenic good cholesterol. It is involved in reverse transport of lipids. Epidemiological studies have found inverse relationship of HDL-C and coronary heart disease (CHD risk. When grouped according to HDL-C, subjects having HDL-C more than 60 mg/dL had lesser risk of CHD than those having HDL-C of 40-60 mg/dL, who in turn had lesser risk than those who had HDL-C less than 40 mg/dL. No upper limit for beneficial effect of HDL-C on CHD risk has been identified. The goals of treating patients with low HDL-C have not been firmly established. Though many drugs are known to improve HDL-C concentration, statins are proven to improve CHD risk and mortality. Cholesteryl ester transfer protein (CETP is involved in metabolism of HDL-C and its inhibitors are actively being screened for clinical utility. However, final answer is still awaited on CETP-inhibitors.

  2. Obtention of scintillography images by low density lipoproteins labelled with technetium 99

    International Nuclear Information System (INIS)

    Silva, S.; Coelho, I.; Zanardo, E.; Pileggi, F.; Meneguethi, C.; Maranhao, R.C.

    1992-01-01

    The low density lipoproteins carry the most part of the cholesterol in the blood plasma. These lipoproteins are labelled with technetium-99-m and have been used for obtaining images in nuclear medicine. The introduction of this technique is presented, aiming futures clinical uses. Scintillographic images are obtained 25 minutes and 24 hours after the injection of 3 m Ci of low density lipoproteins - technetium-99 m in rabbits. (C.G.C.)

  3. Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

    Directory of Open Access Journals (Sweden)

    Takayama Shuzo

    2010-12-01

    Full Text Available Abstract Background The aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults. Methods This cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89 years and 779 women aged 60 ± 12 (range, 21-88 years. The study sample were 1,042 (74.8% non-obese (BMI 2 and 351 (25.2% overweight (BMI ≥ 25 kg/m2 subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR of at least 2.5. The areas under the curve (AUC of the receiver operating characteristic curves (ROC were used to compare the power of these serum markers. Results In non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C/high-density lipoprotein cholesterol (HDL-C ratio of 0.74 (95% confidence interval (CI, 0.66-0.80. The HDL-C, triglyceride (TG/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38, 0.69 (95% CI, 0.62-0.75 and 0.69 (95% CI, 0.62-0.75, respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71 and 0.64 (0.57-0.70, respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20, ≥2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio. Conclusion In non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.

  4. Current and future pharmacologic options for the management of patients unable to achieve low-density lipoprotein-cholesterol goals with statins

    NARCIS (Netherlands)

    El Harchaoui, Karim; Akdim, Fatima; Stroes, Erik S. G.; Trip, Mieke D.; Kastelein, John J. P.

    2008-01-01

    Low-density lipoprotein-cholesterol (LDL-C) lowering is the mainstay of the current treatment guidelines in the management of cardiovascular risk. HMG-CoA reductase inhibitors (statins) are Currently the most effective LDL-C-lowering drugs. However, a substantial number of patients do not reach

  5. Transfer of plasma lipoprotein components and of plasma proteins into aortas of cholesterol-fed rabbits. Molecular size as a determinant of plasma lipoprotein influx

    International Nuclear Information System (INIS)

    Stender, S.; Zilversmit, D.B.

    1981-01-01

    The arterial influx of esterified and free cholesterol from low density lipoproteins and very low density lipoproteins in 20 hypercholesterolemic rabbits was measured simultaneously by the use of lipoproteins labeled in vivo with [ 3 H]- and [ 14 C]-cholesterol. The simultaneous arterial influx of either [ 3 H]-leucine-labeled very low density lipoproteins, low density lipoproteins, high density lipoproteins, or plasma proteins was also measured in each rabbit. The arterial influx was calculated as intimal clearance, i.e., the influx of a given fraction divided by its plasma concentration. The intimal clearance of low density lipoprotein esterified cholesterol was equal to that for the apolipoproteins of that fraction, which is compatible with an arterial influx of intact low density lipoprotein molecules. The intimal clearance of very low density apolipoprotein or cholesteryl ester was less than that for low density lipoprotein, whereas high density lipoprotein and albumin clearances exceeded low density lipoprotein clearance by 1.5- to 3-fold. The intimal clearances of plasma proteins, high density, low density, and very low density lipoproteins decreased linearly with the logarithm of the macromolecular diameter. This indicates that the arterial influx of three plasma lipoprotein fractions and of plasma proteins proceeds by similar mechanisms. Apparently the relative intimal clearances of lipoproteins are more dependent on their size relative to pores or vesicular diameters at the plasma-artery interface than on specific interactions between lipoproteins and the arterial intimal surface

  6. A 90 minute soccer match decreases triglyceride and low density lipoprotein but not high-density lipoprotein and cholesterol levels

    Directory of Open Access Journals (Sweden)

    Nader - Rahnama

    2009-11-01

    Full Text Available

    • BACKGROUND: The association between the lipid profiles level and the incidence and severity of coronary heart disease (CHD is very pronounced in epidemiological studies, and an inverse relation between physical fitness and the incidence of coronary heart disease has been observed in many studies. The aim of this study was to investigate the impact of a soccer match on lipid parameters of professional soccer players.
    • METHODS: Twenty two professional soccer players participated in the study. Blood (10ml for determination of lipid profiles was obtained at rest and immediately after a 90 minute soccer match. Lipid parameters were measured using Boehringer Mannheim kits and Clinilab and BioMerieux analyser.
    • RESULTS: The results of this study showed that the triglyceride was significantly higher before the match than afterwards (159.09 ± 58.2 vs. 88.63 ± 34.1 mg/dl, p < 0.001, whereas the low-density lipoprotein (LDL was lower before the match than after it (98.04 ± 28.9 vs. 112.31 ± 30.5 mg/dl. Moreover, there were no significant differences in cholesterol concentration (171.4 ± 30.28 mg/dl vs. 173.18 ± 32.75 mg/dl and high-density lipoprotein (HDL concentration (34.04 ± 5.58 mg/dl vs. 34.4 ± 4.6 mg/dl between before and after the match.
    • CONCLUSIONS: Although the soccer competitive match has no favourable acute effect on lipid

    • Drugs targeting high-density lipoprotein cholesterol for coronary artery disease management.

      Science.gov (United States)

      Katz, Pamela M; Leiter, Lawrence A

      2012-01-01

      Many patients remain at high risk for future cardiovascular events despite levels of low-density lipoprotein cholesterol (LDL-C) at, or below, target while taking statin therapy. Much effort is therefore being focused on strategies to reduce this residual risk. High-density lipoprotein cholesterol (HDL-C) is a strong, independent, inverse predictor of coronary heart disease risk and is therefore an attractive therapeutic target. Currently available agents that raise HDL-C have only modest effects and there is limited evidence of additional cardiovascular risk reduction on top of background statin therapy associated with their use. It was hoped that the use of cholesteryl ester transfer protein (CETP) inhibitors would provide additional benefit, but the results of clinical outcome studies to date have been disappointing. The results of ongoing trials with other CETP inhibitors that raise HDL-C to a greater degree and also lower LDL-C, as well as with other emerging therapies are awaited. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

    • Pharmacologic management of isolated low high-density lipoprotein syndrome.

      Science.gov (United States)

      Bermúdez, Valmore; Cano, Raquel; Cano, Clímaco; Bermúdez, Fernando; Arraiz, Nailet; Acosta, Luis; Finol, Freddy; Pabón, María Rebeca; Amell, Anilsa; Reyna, Nadia; Hidalgo, Joaquin; Kendall, Paúl; Manuel, Velasco; Hernández, Rafael

      2008-01-01

      High-density lipoprotein (HDL) cholesterol is a heterogeneous group of lipoproteins exhibiting a variety of properties like prostacyclin production stimulation, decrease in platelet aggregation, endothelial cell apoptosis inhibition, and low-density lipoprotein oxidation blockade. Epidemiologic studies have shown an inverse relation between HDL cholesterol levels and cardiovascular risk. Low HDL cholesterol is associated with increased risk for myocardial infarction, stroke, sudden death, peripheral artery disease, and postangioplasty restenosis. In contrast, high HDL levels are associated with longevity and protection against atherosclerotic disease development. Given the evolving epidemic of obesity, diabetes mellitus, and metabolic syndrome, the prevalence of low HDL will continue to rise. In the United States, low HDL is present in 35% of men, 15% of women, and approximately 63% of patients with coronary artery disease. Data extracted from the Framingham study highlight that 1-mg increase in HDL levels decreases by 2% to 3% the risk of cardiovascular disease. There is no doubt regarding clinical importance about isolated low HDL, but relatively few clinicians consider a direct therapeutic intervention of this dyslipidemia. In this sense, lifestyle measures should be the first-line strategy to manage low HDL levels. On the other hand, pharmacologic options include niacin, fibrates, and statins. Fibrates appear to reduce risk preferentially in patients with low HDL with metabolic syndrome, whereas statins reduce risk across all levels of HDL. Torcetrapib, a cholesteryl esters transfer protein inhibitor, represented a hope to raise this lipoprotein; however, all clinical trials on this drug had ceased after ILLUMINATE, RADIANCE and ERASE trials had recorded an increase in mortality, rates of myocardial infarction, angina, and heart failure. In the near future, drugs as beta-glucans, Apo-A1 mimetic peptides, and ACAT inhibitors, are the new promises to treat this

    • The Influence of Decreased Levels of High Density Lipoprotein ...

      African Journals Online (AJOL)

      very low density lipoprotein cholesterol, and triglyceride were assayed. ... Abiodun and Gwarzo: Association of high density lipoprotein cholesterol with haemolysis in sickle cell disease ... analyses were carried out to determine the correlation.

    • HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events

      NARCIS (Netherlands)

      Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles

      2007-01-01

      BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. METHODS: A post hoc analysis of the recently

    • Epidemiological reference ranges for low-density lipoprotein ...

      African Journals Online (AJOL)

      Although there is widespread acceptance that total cholesterol (TC) value reference ranges should be based on epidemiological rather than statistical considerations, the epidemiological action limits for Iow-density lipoprotein cholesterol (LDL-C) are still incomplete and only statistical reference ranges for apolipoprotein B ...

    • Low fasting low high-density lipoprotein and postprandial lipemia

      Directory of Open Access Journals (Sweden)

      Sorodila Konstandina

      2004-07-01

      Full Text Available Abstract Background Low levels of high density lipoprotein (HDL cholesterol and disturbed postprandial lipemia are associated with coronary heart disease. In the present study, we evaluated the variation of triglyceride (TG postprandially in respect to serum HDL cholesterol levels. Results Fifty two Greek men were divided into 2 main groups: a the low HDL group (HDL p = 0.002. The low HDL group had significantly higher TG at 4, 6 and 8 h postprandially compared to the controls (p = 0.006, p = 0.002, and p p = 0.017 compared to the matched-control group. ROC analysis showed that fasting TG ≥ 121 mg/dl have 100% sensitivity and 81% specificity for an abnormal TG response (auc = 0.962, p Conclusions The delayed TG clearance postprandially seems to result in low HDL cholesterol even in subjects with low fasting TG. The fasting TG > 121 mg/dl are predictable for abnormal response to fatty meal.

    • The biology of PCSK9 from the endoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol

      Directory of Open Access Journals (Sweden)

      Poirier S

      2013-10-01

      Full Text Available Steve Poirier,1,2 Gaétan Mayer1–31Laboratory of Molecular Cell Biology, Montreal Heart Institute, Montréal, QC, Canada; 2Départements de Pharmacologie, 3Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC, CanadaAbstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9 directly binds to the epidermal growth factor-like repeat A domain of low-density lipoprotein receptor and induces its degradation, thereby controlling circulating low-density lipoprotein cholesterol (LDL-C concentration. Heterozygous loss-of-function mutations in PCSK9 can decrease the incidence of coronary heart disease by up to 88%, owing to lifelong reduction of LDL-C. Moreover, two subjects with PCSK9 loss-of-function mutations on both alleles, resulting in a total absence of functional PCSK9, were found to have extremely low circulating LDL-C levels without other apparent abnormalities. Accordingly, PCSK9 could represent a safe and effective pharmacological target to increase clearance of LDL-C and to reduce the risk of coronary heart disease. Recent clinical trials using anti-PCSK9 monoclonal antibodies that block the PCSK9:low-density lipoprotein receptor interaction were shown to considerably reduce LDL-C levels by up to 65% when given alone and by up to 72% in patients already receiving statin therapy. In this review, we will discuss how major scientific breakthroughs in PCSK9 cell biology have led to the development of new and forthcoming LDL-C-lowering pharmacological agents.Keywords: PCSK9, LDLR, LDL-cholesterol, lipoproteins, coronary heart disease, inhibitors, monoclonal antibody therapy

    • Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus.

      Science.gov (United States)

      Gutierrez, Maria J; Rosenberg, Noah L; Macdougall, Diane E; Hanselman, Jeffrey C; Margulies, Janice R; Strange, Poul; Milad, Mark A; McBride, Scott J; Newton, Roger S

      2014-03-01

      8-Hydroxy-2,2,14,14-tetramethylpentadecanedioic acid (ETC-1002) is a small molecule with a unique mechanism of action shown in nonclinical studies to modulate pathways of cholesterol, fatty acid, and carbohydrate metabolism. In previous phase 2 clinical trials, once daily oral treatment with ETC-1002 significantly reduced low-density lipoprotein-cholesterol in patients with hypercholesterolemia. In this trial, the lipid-lowering efficacy of ETC-1002 was evaluated in patients with type 2 diabetes mellitus and hypercholesterolemia. Additional cardiometabolic biomarkers, including glycemic measures, were also assessed. A single-center, double-blind, placebo-controlled trial evaluated 60 patients with type 2 diabetes mellitus and elevated low-density lipoprotein-cholesterol. Patients discontinued all diabetes mellitus and lipid-regulating drugs and were randomized to receive ETC-1002 80 mg QD for 2 weeks followed by 120 mg QD for 2 weeks or placebo for 4 weeks. ETC-1002 lowered low-density lipoprotein-cholesterol levels by 43±2.6% (least squares mean±SE), compared with a reduction of 4±2.5% by placebo at day 29 (Pdiabetes mellitus and hypercholesterolemia without worsening glycemic control. ETC-1002 was well tolerated in this population. http://www.clinicaltrials.gov. Unique identifier: NCT# 01607294.

    • [A history and review of cholesterol ester transfer protein inhibitors and their contribution to the understanding of the physiology and pathophysiology of high density lipoprotein].

      Science.gov (United States)

      Corral, Pablo; Schreier, Laura

      2014-01-01

      There is irrefutable evidence that statins reduce the risk of cardiovascular events in a magnitude proportional to the intensity of the decrease in cholesterol transport by the low density lipoproteins. Despite this great advance there is still a residual risk of cardiovascular events. For this reason, an increase in the levels of high density lipoprotein is considered in order to boost the main action of this lipoprotein, which is reverse cholesterol transport. Distinct classes of evidence (epidemiological, genetic, and pathophysiological) show that the inhibition and/or modulation of cholesterol ester transfer protein increases plasma high density lipoprotein-cholesterol levels. The main reason for presenting this review is to look at the physiology of cholesterol ester transfer protein, its interrelationship with high density lipoproteins, and to give an update on the development of different cholesterol ester transfer protein inhibitor/modulator molecules. Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.

    • INHIBITION OF HUMAN LOW-DENSITY LIPOPROTEINS OXIDATION BY Hibiscus radiatus CUV. CALYCES EXTRACT

      Directory of Open Access Journals (Sweden)

      Hernawan Hernawan

      2010-06-01

      Full Text Available Hibiscus radiatus Cuv calyces extracts rich in polyphenols was screened for their potential to inhibit oxidation of human low-density lipoproteins-cholesterol (LDL-C in vitro. The inhibition of LDL-C oxidation (antioxidant activity was determined by measuring the formation of conjugated dienes and thiobarbituric acid reagent substances (TBARS. LDL-C oxidation was carried out in the presence of H. radiatus Cuv calyces extract (20 and 50 μM. CuSO4 (10 μM was used as the oxidation initiator and  butylated hydroxytoluene (BHT at 50 μM was used as standard antioxidant. The protective effect of H. radiatus Cuv. calyces extract toward human low-density lipoproteins, complex lipid system was  demonstrated by significant increase lag time (> 103 min, diminished of the propagation rate (44 %, and diminution of conjugated dienes formation 59.42 % (50 μM compared to control.   Keywords: antioxidant, conjugated dienes, Hibiscus radiatus Cuv, low-density lipoproteins-cholesterol

    • Suppression of cholesterol synthesis in cultured fibroblasts from a patient with homozygous familial hypercholesterolemia by her own low density lipoprotein density fraction. A possible role of apolipoprotein E

      NARCIS (Netherlands)

      Havekes, L.; Vermeer, B.J.; Wit, E. de

      1980-01-01

      The suppression of cellular cholesterol synthesis by low density lipoprotein (LDL) from a normal and from a homozygous familial hypercholesterolemic subject was measured on normal fibroblasts and on fibroblasts derived from the same homozygous familial hypercholesterolemic patient. On normal

    • Intracellular transport of low density lipoprotein-derived cholesterol is defective in Niemann-Pick type C fibroblasts

      International Nuclear Information System (INIS)

      Liscum, L.; Ruggiero, R.M.; Faust, J.R.

      1989-01-01

      Niemann-Pick disease type C (NPC) is characterized by substantial intracellular accumulation of unesterified cholesterol. The accumulation of unesterified cholesterol in NPC fibroblasts cultured with low density lipoprotein (LDL) appears to result from the inability of LDL to stimulate cholesterol esterification in addition to impaired LDL-mediated downregulation of LDL receptor activity and cellular cholesterol synthesis. Although a defect in cholesterol transport in NPC cells has been inferred from previous studies, no experiments have been reported that measure the intracellular movement of LDL-cholesterol specifically. We have used four approaches to assess intracellular cholesterol transport in normal and NPC cells and have determined the following: (a) mevinolin-inhibited NPC cells are defective in using LDL-cholesterol for growth. However, exogenously added mevalonate restores cell growth equally in normal and NPC cells; (b) the transport of LDL-derived [3H]cholesterol to the plasma membrane is slower in NPC cells, while the rate of appearance of [3H]acetate-derived, endogenously synthesized [3H]cholesterol at the plasma membrane is the same for normal and NPC cells; (c) in NPC cells, LDL-derived [3H]cholesterol accumulates in lysosomes to higher levels than normal, resulting in defective movement to other cell membranes; and (d) incubation of cells with LDL causes an increase in cholesterol content of NPC lysosomes that is threefold greater than that observed in normal lysosomes. Our results indicate that a cholesterol transport defect exists in NPC that is specific for LDL-derived cholesterol

    • The prevalence and correlates of subclinical atherosclerosis among adults with low-density lipoprotein cholesterol ELSA-Brasil).

      Science.gov (United States)

      Al Rifai, Mahmoud; Martin, Seth S; McEvoy, John W; Nasir, Khurram; Blankstein, Ron; Yeboah, Joseph; Miedema, Michael; Shea, Steven J; Polak, Joseph F; Ouyang, Pamela; Blumenthal, Roger S; Bittencourt, Marcio; Bensenor, Isabela; Santos, Raul D; Duncan, Bruce B; Santos, Itamar S; Lotufo, Paulo A; Blaha, Michael J

      2018-07-01

      The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4 th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis. Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively). Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking. Copyright © 2018 Elsevier B.V. All rights reserved.

    • Common low-density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein cholesterol in circumpolar inuit populations.

      Science.gov (United States)

      Dubé, Joseph B; Wang, Jian; Cao, Henian; McIntyre, Adam D; Johansen, Christopher T; Hopkins, Scarlett E; Stringer, Randa; Hosseinzadeh, Siyavash; Kennedy, Brooke A; Ban, Matthew R; Young, T Kue; Connelly, Philip W; Dewailly, Eric; Bjerregaard, Peter; Boyer, Bert B; Hegele, Robert A

      2015-02-01

      Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p.G116S and p.R730W. Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6×10(-49)), which was >3× larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34-3.90; P=1.7×10(-17)), but did not have classical familial hypercholesterolemia. In vitro, p.G116S showed 60% reduced ligand-binding activity compared with wild-type receptor. In contrast, p.R730W was associated with neither LDL cholesterol level nor altered in vitro activity. LDLR p.G116S is thus unique: a common dysfunctional variant in Inuit whose large effect on LDL cholesterol may have public health implications. © 2014 American Heart Association, Inc.

  1. Genetically elevated apolipoprotein A-I, high-density lipoprotein cholesterol levels, and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Lundegaard, Christiane; Tybjærg-Hansen, Anne; Grande, Peer

    2010-01-01

    Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD).......Epidemiologically, levels of high-density lipoprotein (HDL) cholesterol and its major protein constituent, apolipoprotein A-I (apoA-I), are inversely related to risk of ischemic heart disease (IHD)....

  2. On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy

    DEFF Research Database (Denmark)

    Mora, Samia; Glynn, Robert J; Boekholdt, S Matthijs

    2012-01-01

    The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), tri...

  3. Rethinking reverse cholesterol transport and dysfunctional high-density lipoproteins.

    Science.gov (United States)

    Gillard, Baiba K; Rosales, Corina; Xu, Bingqing; Gotto, Antonio M; Pownall, Henry J

    2018-04-12

    Human plasma high-density lipoprotein cholesterol concentrations are a negative risk factor for atherosclerosis-linked cardiovascular disease. Pharmacological attempts to reduce atherosclerotic cardiovascular disease by increasing plasma high-density lipoprotein cholesterol have been disappointing so that recent research has shifted from HDL quantity to HDL quality, that is, functional vs dysfunctional HDL. HDL has varying degrees of dysfunction reflected in impaired reverse cholesterol transport (RCT). In the context of atheroprotection, RCT occurs by 2 mechanisms: one is the well-known trans-hepatic pathway comprising macrophage free cholesterol (FC) efflux, which produces early forms of FC-rich nascent HDL (nHDL). Lecithin:cholesterol acyltransferase converts HDL-FC to HDL-cholesteryl ester while converting nHDL from a disc to a mature spherical HDL, which transfers its cholesteryl ester to the hepatic HDL receptor, scavenger receptor B1 for uptake, conversion to bile salts, or transfer to the intestine for excretion. Although widely cited, current evidence suggests that this is a minor pathway and that most HDL-FC and nHDL-FC rapidly transfer directly to the liver independent of lecithin:cholesterol acyltransferase activity. A small fraction of plasma HDL-FC enters the trans-intestinal efflux pathway comprising direct FC transfer to the intestine. SR-B1 -/- mice, which have impaired trans-hepatic FC transport, are characterized by high plasma levels of a dysfunctional FC-rich HDL that increases plasma FC bioavailability in a way that produces whole-body hypercholesterolemia and multiple pathologies. The design of future therapeutic strategies to improve RCT will have to be formulated in the context of these dual RCT mechanisms and the role of FC bioavailability. Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  4. Effect of apolipoprotein E-free high density lipoproteins on cholesterol metabolism in cultured pig hepatocytes

    International Nuclear Information System (INIS)

    Bachorik, P.S.; Virgil, D.G.; Kwiterovich, P.O. Jr.

    1987-01-01

    We studied cholesterol synthesis from [ 14 C]acetate, cholesterol esterification from [ 14 C]oleate, and cellular cholesterol and cholesteryl ester levels after incubating cells with apoE-free high density lipoproteins (HDL) or low density lipoproteins (LDL). LDL suppressed synthesis by up to 60%, stimulated esterification by up to 280%, and increased cell cholesteryl ester content about 4-fold. Esterification increased within 2 h, but synthesis was not suppressed until after 6 h. ApoE-free HDL suppressed esterification by about 50% within 2 h. Cholesterol synthesis was changed very little within 6 h, unless esterification was maximally suppressed; synthesis was then stimulated about 4-fold. HDL lowered cellular unesterified cholesterol by 13-20% within 2 h and promoted the removal of newly synthesized cholesterol and cholesteryl esters. These changes were transient; by 24 h, both esterification and cellular unesterified cholesterol returned to control levels, and cholesteryl esters increased 2-3-fold. HDL core lipid was taken up selectively from 125 I-labeled [ 3 H]cholesteryl ester- and ether-labeled HDL. LDL core lipid uptake was proportional to LDL apoprotein uptake. The findings suggest that 1) the cells respond initially to HDL or LDL with changes in esterification, and 2) HDL mediates both the removal of free cholesterol from the cell and the delivery of HDL cholesteryl esters to the cell

  5. Comparison of a direct enzymatic assay and polyacrylamide tube gel electrophoresis for measurement of small, dense low-density lipoprotein cholesterol.

    Science.gov (United States)

    Vanavanan, Somlak; Srisawasdi, Pornpen; Rochanawutanon, Mana; Kerdmongkol, Jirapa; Kroll, Martin H

    2015-01-01

    Small, dense low-density lipoprotein cholesterol (sdLDL-C) has been linked to the progression of cardiovascular disease. We compared two methods for determination of sdLDL-C, a direct enzymatic (ENZ) method and a polyacrylamide tube gel electrophoresis (PGE) assay, and investigated the associations of both sdLDL-C measurements with metabolic syndrome. We analyzed 242 patient sera for sdLDL and atherosclerosis-related markers. The PGE method separates the intermediate-density lipoprotein particles into three midbands (MID-A to MID-C) and the LDL particles into seven subfractions (LDL1 to LDL7); the sdLDL-PGE result is calculated as the sum of cholesterol concentrations from LDL3 to LDL7. The regression equation for sdLDL-C was [ENZmmol/L]=0.779[PGE]+0.67, r=0.713. ENZ showed higher sdLDL-C concentrations than PGE (0.86±0.33 vs. 0.24±0.32 mmol/L); however, the difference was not associated with sdLDL-C concentration (p=0.290). sdLDL-C, as measured with the enzymatic assay, exhibited significant positive correlations with very-low-density lipoprotein, MID-C, MID-B, and LDL2 (all p0.600). The ENZ and PGE methods yielded similar patterns of correlation between sdLDL-C, and atherosclerosis-related markers. Using logistic regression, sdLDL-ENZ and apolipoprotein B were identified as significant predictors of metabolic syndrome (p<0.03). The ENZ assay for sdLDL-C correlated well with the PGE method. The ENZ method measures a broader range of atherogenic lipoprotein particles than PGE and has the potential to identify subjects with vascular risk, thus contributing in directing specific interventions for cardiovascular prevention.

  6. Impact of hormonal contraception and weight loss on high-density lipoprotein cholesterol efflux and lipoprotein particles in women with polycystic ovary syndrome.

    Science.gov (United States)

    Dokras, Anuja; Playford, Martin; Kris-Etherton, Penny M; Kunselman, Allen R; Stetter, Christy M; Williams, Nancy I; Gnatuk, Carol L; Estes, Stephanie J; Sarwer, David B; Allison, Kelly C; Coutifaris, Christos; Mehta, Nehal; Legro, Richard S

    2017-05-01

    To study the effects of oral contraceptive pills (OCP), the first-line treatment for PCOS, on high-density lipoprotein cholesterol (HDL-C) function (reverse cholesterol efflux capacity) and lipoprotein particles measured using nuclear magnetic resonance spectroscopy in obese women. Secondary analysis of a randomized controlled trial (OWL-PCOS) of OCP or Lifestyle (intensive Lifestyle modification) or Combined (OCP + Lifestyle) treatment groups for 16 weeks. Eighty-seven overweight/obese women with PCOS at two academic centres. Change in HDL-C efflux capacity and lipoprotein particles. High-density lipoprotein cholesterol efflux capacity increased significantly at 16 weeks in the OCP group [0·11; 95% confidence interval (CI) 0·03, 0·18, P = 0·008] but not in the Lifestyle (P = 0·39) or Combined group (P = 0·18). After adjusting for HDL-C and TG levels, there was significant mean change in efflux in the Combined group (0·09; 95% CI 0·01, 0·15; P = 0·01). Change in HDL-C efflux correlated inversely with change in serum testosterone (r s = -0·21; P = 0·05). In contrast, OCP use induced an atherogenic low-density lipoprotein cholesterol (LDL-C) profile with increase in small (P = 0·006) and large LDL-particles (P = 0·002). Change in small LDL-particles correlated with change in serum testosterone (r s = -0·31, P = 0·009) and insulin sensitivity index (ISI; r s = -0·31, P = 0·02). Both Lifestyle and Combined groups did not show significant changes in the atherogenic LDL particles. Oral contraceptive pills use is associated with improved HDL-C function and a concomitant atherogenic LDL-C profile. Combination of a Lifestyle program with OCP use improved HDL-C function and mitigated adverse effects of OCP on lipoproteins. Our study provides evidence for use of OCP in overweight/obese women with PCOS when combined with Lifestyle changes. © 2017 John Wiley & Sons Ltd.

  7. Acetaldehyde binding increases the catabolism of rat serum low-density lipoproteins

    International Nuclear Information System (INIS)

    Savolainen, M.J.; Baraona, E.; Lieber, C.S.

    1987-01-01

    Acetaldehyde was found to form adducts with rat serum lipoproteins. The binding of [ 14 C]acetaldehyde to lipoproteins was studied at low concentrations which are known to exist during ethanol oxidation. The amount of lipoprotein adducts was a linear function of acetaldehyde concentration up to 250 μM. Incubation of rat plasma low-density lipoproteins (LDL) with 200 μM acetaldehyde increased the disappearance rate of the 3 H-label from the cholesterol ester moiety of LDL injected into normal rats. The data show that even low concentrations of acetaldehyde are capable of affecting LDL metabolism. These findings may provide an explanation for the low concentrations of serum LDL in alcoholics. The alcohol-induced hyperlipidemia includes either a lack of increase or a decrease in the low-density lipoprotein (LDL) concentration, but the underlying mechanism is not known. It has been shown previously, that the acetylation of lysine residues of LDL apoprotein (apoB) by acetanhydride leads to rapid uptake of LDL particles by macrophages through a non-LDL receptor pathway. Since acetaldehyde, the first toxic metabolite of ethanol, is a chemically reactive compound capable of binding to proteins, they tested whether acetaldehyde forms adducts with serum lipoproteins and subsequently alters the catabolism of LDL. 19 references, 2 figures, 1 table

  8. Effects of low-dose simvastatin on the distribution of plasma cholesterol and oxidized low-density lipoprotein in three ultra-centrifugally separated low-density lipoprotein subfractions: 12- month, open-label trial.

    Science.gov (United States)

    Homma, Yasuhiko; Michishita, Ichiro; Hayashi, Hiroshi; Shigematsu, Hiroshi

    2010-10-27

    The effects of statins on the distribution of oxidized LDL in plasma LDL subfractions have not been well defined. Effects of 12-month treatment with low-dose simvastatin on the distribution of cholesterol and oxidized LDL in 3 ultracentrifugally separated plasma LDL subfractions were compared in patients with hypercholesterolemia. Simvastatin was administered to 30 hypercholesterolemic subjects for 12 months at an initial dose of 5 mg/day, which was increased to 20 mg/day via 10mg/day to decrease plasma LDL-cholesterol (C) lower than 130 mg/dL. Simvastatin dose was fixed after 3 months of treatment. The amounts of cholesterol and oxidized LDL in 3 ultracentrifugally separated plasma LDL subfractions were compared between 0 and 12 months of treatment. The distribution of ox-LDL skewed to denser LDL fractions, compared with cholesterol in plasma LDL subfractions. Plasma cholesterol in low-density LDL, medium-density LDL and high-density LDL decreased significantly by 31%, 30%, and 25%, respectively (pLDL was decreased from 70 U/L to 56 U/L in medium-density LDL (p=0.042). Oxidized LDL in low-density LDL and high-density LDL did not change significantly after 12 months of treatment. Treatment with low-dose simvastatin decreased plasma cholesterol in 3 LDL subfractions and oxidized LDL in medium-density LDL. The decrease of oxidized LDL seemed to be not due to the decrease of cholesterol in plasma LDL subfractions because the decreasing patterns of cholesterol and ox-LDL were different in 3 LDL subfractions.

  9. Evidence for low high-density lipoprotein cholesterol levels in Australian indigenous peoples: a systematic review.

    Science.gov (United States)

    Lyons, Jasmine G; O'Dea, Kerin; Walker, Karen Z

    2014-06-02

    Low plasma high-density lipoprotein cholesterol (HDL-C) levels are a strong, independent, but poorly understood risk factor for cardiovascular disease (CVD). Although this atherogenic lipid abnormality has been widely reported in Australia's Indigenous peoples, Aboriginal and Torres Strait Islanders, the evidence has not come under systematic review. This review therefore examines published data for Indigenous Australians reporting 1) mean HDL-C levels for both sexes and 2) factors associated with low HDL-C. PubMed, Medline and Informit ATSI Health databases were systematically searched between 1950 and 2012 for studies on Indigenous Australians reporting mean HDL-C levels in both sexes. Retrieved studies were evaluated by standard criteria. Low HDL-C was defined as: Indigenous populations living in rural and remote communities. Inverse associations between HDL-C and central obesity, diabetes prevalence and inflammatory markers suggest a particularly adverse CVD risk factor profile. An absence of sex dichotomy in HDL-C levels warrants further investigation.

  10. High triglycerides and low high-density lipoprotein cholesterol lipid profile in rheumatoid arthritis: A potential link among inflammation, oxidative status, and dysfunctional high-density lipoprotein.

    Science.gov (United States)

    Rodríguez-Carrio, Javier; Alperi-López, Mercedes; López, Patricia; López-Mejías, Raquel; Alonso-Castro, Sara; Abal, Francisco; Ballina-García, Francisco J; González-Gay, Miguel Á; Suárez, Ana

    The interactions between inflammation and lipid profile in rheumatoid arthritis (RA) are poorly understood. The lipid profile study in RA has been biased toward lipoprotein levels, whereas those of triglycerides (TGs) and lipoprotein functionality have been underestimated. Since recent findings suggest a role for TG and TG-rich lipoproteins (TRL) on inflammation, we aimed to evaluate a combined lipid profile characterized by high TG and low high-density lipoprotein cholesterol levels (TG high HDL low ) in RA. Lipid profiles were analyzed in 113 RA patients, 113 healthy controls, and 27 dyslipemic subjects. Levels of inflammatory mediators, paraoxonase-1 (PON1) activity, and total antioxidant capacity were quantified in serum. PON1-rs662 status was evaluated by real-time polymerase chain reaction. The TG high HDL low profile was detected in 29/113 RA patients. Although no differences in prevalence compared with healthy controls or dyslipemic subjects were observed, this profile was associated with increased tumor necrosis factor α (P = .004), monocyte chemotactic protein (P = .004), interferon-gamma-inducible protein-10 (P = .018), and leptin (P < .001) serum levels in RA, where decreased PON1 activity and total antioxidant capacity were found. TG high HDL low prevalence was lower among anti-TNFα-treated patients (P = .004). When RA patients were stratified by PON1-rs662 status, these associations remained in the low-activity genotype (QQ). Finally, a poor clinical response on TNFα blockade was related to an increasing prevalence of the TG high HDL low profile over treatment (P = .021) and higher TRL levels at baseline (P = .042). The TG high HDL low profile is associated with systemic inflammation, decreased PON1 activity, and poor clinical outcome on TNFα blockade in RA, suggesting a role of TRL and HDL dysfunction as the missing link between inflammation and lipid profile. Copyright © 2017 National Lipid Association. Published by Elsevier Inc

  11. The Relationship between the Triglyceride to High-Density Lipoprotein Cholesterol Ratio and Metabolic Syndrome.

    Science.gov (United States)

    Shin, Hyun-Gyu; Kim, Young-Kwang; Kim, Yong-Hwan; Jung, Yo-Han; Kang, Hee-Cheol

    2017-11-01

    Metabolic syndrome is associated with cardiovascular diseases and is characterized by insulin resistance. Recent studies suggest that the triglyceride/high-density lipoprotein cholesterol (TG/HDLC) ratio predicts insulin resistance better than individual lipid levels, including TG, total cholesterol, low-density lipoprotein cholesterol (LDLC), or HDLC. We aimed to elucidate the relationship between the TG/HDLC ratio and metabolic syndrome in the general Korean population. We evaluated the data of adults ≥20 years old who were enrolled in the Korean National Health and Nutrition Examination Survey in 2013 and 2014. Subjects with angina pectoris, myocardial infarction, stroke, or cancer were excluded. Metabolic syndrome was defined by the harmonized definition. We examined the odds ratios (ORs) of metabolic syndrome according to TG/HDLC ratio quartiles using logistic regression analysis (SAS ver. 9.4; SAS Institute Inc., Cary, NC, USA). Weighted complex sample analysis was also conducted. We found a significant association between the TG/HDLC ratio and metabolic syndrome. The cutoff value of the TG/HDLC ratio for the fourth quartile was ≥3.52. After adjustment, the OR for metabolic syndrome in the fourth quartile compared with that of the first quartile was 29.65 in men and 20.60 in women (Pmetabolic syndrome.

  12. Role of Hepatic Lipase and Endothelial Lipase in High-Density Lipoprotein-Mediated Reverse Cholesterol Transport

    NARCIS (Netherlands)

    Annema, Wijtske; Tietge, Uwe J. F.

    Reverse cholesterol transport (RCT) constitutes a key part of the atheroprotective properties of high-density lipoproteins (HDL). Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol levels. Although overexpression of EL decreases overall

  13. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.

    Science.gov (United States)

    Gordon, D J; Probstfield, J L; Garrison, R J; Neaton, J D; Castelli, W P; Knoke, J D; Jacobs, D R; Bangdiwala, S; Tyroler, H A

    1989-01-01

    The British Regional Heart Study (BRHS) reported in 1986 that much of the inverse relation of high-density lipoprotein cholesterol (HDLC) and incidence of coronary heart disease was eliminated by covariance adjustment. Using the proportional hazards model and adjusting for age, blood pressure, smoking, body mass index, and low-density lipoprotein cholesterol, we analyzed this relation separately in the Framingham Heart Study (FHS), Lipid Research Clinics Prevalence Mortality Follow-up Study (LRCF) and Coronary Primary Prevention Trial (CPPT), and Multiple Risk Factor Intervention Trial (MRFIT). In CPPT and MRFIT (both randomized trials in middle-age high-risk men), only the control groups were analyzed. A 1-mg/dl (0.026 mM) increment in HDLC was associated with a significant coronary heart disease risk decrement of 2% in men (FHS, CPPT, and MRFIT) and 3% in women (FHS). In LRCF, where only fatal outcomes were documented, a 1-mg/dl increment in HDLC was associated with significant 3.7% (men) and 4.7% (women) decrements in cardiovascular disease mortality rates. The 95% confidence intervals for these decrements in coronary heart and cardiovascular disease risk in the four studies overlapped considerably, and all contained the range 1.9-2.9%. HDLC levels were essentially unrelated to non-cardiovascular disease mortality. When differences in analytic methodology were eliminated, a consistent inverse relation of HDLC levels and coronary heart disease event rates was apparent in BRHS as well as in the four American studies.

  14. Predictors of coronary heart disease events among asymptomatic persons with low low-density lipoprotein cholesterol MESA (Multi-Ethnic Study of Atherosclerosis).

    Science.gov (United States)

    Blankstein, Ron; Budoff, Matthew J; Shaw, Leslee J; Goff, David C; Polak, Joseph F; Lima, Joao; Blumenthal, Roger S; Nasir, Khurram

    2011-07-19

    Our aim was to identify risk factors for coronary heart disease (CHD) events among asymptomatic persons with low (≤ 130 mg/dl) low-density lipoprotein cholesterol (LDL-C). Even among persons with low LDL-C, some will still experience CHD events and may benefit from more aggressive pharmacologic and lifestyle therapies. The MESA (Multi-Ethnic Study of Atherosclerosis) is a prospective cohort of 6,814 participants free of clinical cardiovascular disease. Of 5,627 participants who were not receiving any baseline lipid-lowering therapies, 3,714 (66%) had LDL-C ≤ 130 mg/dl and were included in the present study. Unadjusted and adjusted hazard ratios were calculated to assess the association of traditional risk factors and biomarkers with CHD events. To determine if subclinical atherosclerosis markers provided additional information beyond traditional risk factors, coronary artery calcium (CAC) and carotid intima media thickness were each separately added to the multivariable model. During a median follow-up of 5.4 years, 120 (3.2%) CHD events were observed. In unadjusted analysis, age, male sex, hypertension, diabetes mellitus, low high-density lipoprotein cholesterol (HDL-C), high triglycerides, and subclinical atherosclerosis markers (CAC >0; carotid intima media thickness ≥1 mm) predicted CHD events. Independent predictors of CHD events included age, male sex, hypertension, diabetes, and low HDL-C. After accounting for all traditional risk factors, the predictive value of CAC was attenuated but remained highly significant. The relationship of all independent clinical predictors remained robust even after accounting for elevated CAC. Among persons with low LDL-C, older age, male sex, hypertension, diabetes, and low HDL-C are associated with adverse CHD events. Even after accounting for all such variables, the presence of CAC provided incremental prognostic value. These results may serve as a basis for deciding which patients with low LDL-C may be considered for

  15. Oxidation of cholesterol moiety of low density lipoprotein in the presence of human endothelial cells or Cu+2 ions: identification of major products and their effects.

    Science.gov (United States)

    Bhadra, S; Arshad, M A; Rymaszewski, Z; Norman, E; Wherley, R; Subbiah, M T

    1991-04-15

    Oxidation of lipoproteins is believed to play a key role in atherogenesis. In this study, low density lipoproteins (LDL) was subjected to oxidation in the presence of either human umbilical vein endothelial cells or with Cu+2 ions and the major oxides formed were identified. While cholesterol-alpha-epoxide (C-alpha EP) was the major product of cholesterol peroxidation in the presence of endothelial cells, cholest-3,5-dien-7-one (CD) predominated in the presence of Cu+2 ion. Both steroids were identified by gas chromatography/mass spectrometry. HDL cholesterol was resistant to oxidation. When tested on human skin fibroblasts in culture C-alpha EP (10 micrograms/ml) caused marked stimulation of 14C-oleate incorporation into cholesterol esters, while CD stimulated cholesterol esterification only mildly. These studies show that a) C-alpha EP is the major peroxidation product of LDL cholesterol moiety in the presence of endothelial cells and b) it causes marked stimulation of cholesterol esterification in cells. C-alpha EP may play a key role in increasing cholesterol esterification noted in atherogenesis.

  16. Hemodynamics alter arterial low-density lipoprotein metabolism

    International Nuclear Information System (INIS)

    Warty, V.S.; Calvo, W.J.; Berceli, S.A.; Pham, S.M.; Durham, S.J.; Tanksale, S.K.; Klein, E.C.; Herman, I.M.; Borovetz, H.S.

    1989-01-01

    We have investigated the role of hemodynamic factors on low-density lipoprotein transport and metabolism in the intact arterial wall. Freshly excised canine carotid blood vessels were exposed to well-defined pulsatile flow in vitro for continuous periods up to 20 hours. We chose to impose the following hemodynamic conditions on our test carotid arteries: normotension, hypertension (at physiologic flow conditions), and hypertension coupled with elevated flow of canine serum perfusate. In several experiments the effect of endothelial denudation was examined in carotid arteries exposed to normotensive pulsatile flow. A trapped ligand method was used for quantitating low-density lipoprotein uptake and metabolism in the arterial wall. The distribution of both intact and degraded low-density lipoprotein fractions was determined from measurements of radiolabelled low-density lipoprotein activity within thin radial sections of perfused arteries. Our results suggest that both hypertensive hemodynamic simulations exacerbate the uptake of low-density lipoprotein within the arterial wall (by a factor of three to nine). The percentage of low-density lipoprotein that undergoes irreversible degradation falls from 41% under normotensive conditions to below 30% when hypertensive conditions are imposed, indicating that degradative processes are not proportionally elevated with the accelerated influx. A similar pattern is observed for deendothelialized vessels

  17. Baseline characteristics of participants in the JUPITER trial, a randomized placebo-controlled primary prevention trial of statin therapy among individuals with low low-density lipoprotein cholesterol and elevated high-sensitivity C-reactive protein

    NARCIS (Netherlands)

    Ridker, Paul M.; Fonseca, Francisco A. H.; Genest, Jacques; Gotto, Antonio M.; Kastelein, John J. P.; Khurmi, Nardev S.; Koenig, Wolfgang; Libby, Peter; Lorenzatti, Alberto J.; Nordestgaard, Borge G.; Shepherd, James; Willerson, James T.; Glynn, Robert J.

    2007-01-01

    The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) is a randomized, double-blind, placebo-controlled primary prevention trial of statin therapy among persons with average to low levels of low-density lipoprotein (LDL) cholesterol

  18. Low plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone deficient and acromegalic men: role in altered high density lipoproteins

    NARCIS (Netherlands)

    Beentjes, JAM; van Tol, A; Sluiter, WJ; Dullaart, RPF

    2000-01-01

    Growth hormone (GH) deficiency and acromegaly may be associated with increased cardiovascular risk. Little is known about alterations in high density lipoproteins (HDL) in these conditions. Lecithin:cholesterol acyl transferase (LCAT) has the ability to esterify free cholesterol (FC) in HDL.

  19. Effect of theobromine consumption on serum lipoprotein profiles in apparently healthy humans with low HDL-cholesterol concentrations

    NARCIS (Netherlands)

    Jacobs, Doris M.; Smolders, Lotte; Lin, Yuguang; Roo, de Niels; Trautwein, Elke A.; Duynhoven, van John; Mensink, Ronald P.; Plat, Jogchum; Mihaleva, Velitchka V.

    2017-01-01

    Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP)

  20. Low density lipoprotein : structure, dynamics, and interactions of apoB-100 with lipids

    NARCIS (Netherlands)

    Murtola, T.; Vuorela, T.A.; Hyvönen, M.T.; Marrink, S.J.; Karttunen, M.E.J.; Vattulainen, I.

    2011-01-01

    Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL's

  1. Identification of miR-185 as a regulator of de novo cholesterol biosynthesis and low density lipoprotein uptake

    Science.gov (United States)

    Yang, Muhua; Liu, Weidong; Pellicane, Christina; Sahyoun, Christine; Joseph, Biny K.; Gallo-Ebert, Christina; Donigan, Melissa; Pandya, Devanshi; Giordano, Caroline; Bata, Adam; Nickels, Joseph T.

    2014-01-01

    Dysregulation of cholesterol homeostasis is associated with various metabolic diseases, including atherosclerosis and type 2 diabetes. The sterol response element binding protein (SREBP)-2 transcription factor induces the expression of genes involved in de novo cholesterol biosynthesis and low density lipoprotein (LDL) uptake, thus it plays a crucial role in maintaining cholesterol homeostasis. Here, we found that overexpressing microRNA (miR)-185 in HepG2 cells repressed SREBP-2 expression and protein level. miR-185-directed inhibition caused decreased SREBP-2-dependent gene expression, LDL uptake, and HMG-CoA reductase activity. In addition, we found that miR-185 expression was tightly regulated by SREBP-1c, through its binding to a single sterol response element in the miR-185 promoter. Moreover, we found that miR-185 expression levels were elevated in mice fed a high-fat diet, and this increase correlated with an increase in total cholesterol level and a decrease in SREBP-2 expression and protein. Finally, we found that individuals with high cholesterol had a 5-fold increase in serum miR-185 expression compared with control individuals. Thus, miR-185 controls cholesterol homeostasis through regulating SREBP-2 expression and activity. In turn, SREBP-1c regulates miR-185 expression through a complex cholesterol-responsive feedback loop. Thus, a novel axis regulating cholesterol homeostasis exists that exploits miR-185-dependent regulation of SREBP-2 and requires SREBP-1c for function. PMID:24296663

  2. Study of Heart and Renal Protection (SHARP) : Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease

    NARCIS (Netherlands)

    Baigent, C.; Landray, M.; Reith, C.; Dasgupta, T.; Emberson, J.; Herrington, W.; Lewis, D.; Mafham, M.; Collins, R.; Collins, R.; Baigent, C.; Landray, M.; Bray, C.; Chen, Y.; Baxter, A.; Young, A.; Hill, M.; Knott, C.; Cass, A.; Feldt-Rasmussen, B.; Fellstroem, B.; Grobbee, R.; Groenhagen-Riska, C.; Haas, M.; Holdaas, H.; Hooi, L. S.; Jiang, L.; Kasiske, B.; Krairittichai, U.; Levin, A.; Massy, Z.; Tesar, V.; Walker, R.; Wanner, C.; Wheeler, D.; Wiecek, A.; Dasgupta, T.; Lewis, D.; Mafham, M.; Majoni, W.; Reith, C.; Simpson, D.; Strony, J.; Musliner, T.; Agodoa, L.; Armitage, J.; Chen, Z.; Craig, J.; de Zeeuw, D.; Gaziano, M.

    Background Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods Patients with

  3. Study of Heart and Renal Protection (SHARP) : Randomized trial to assess the effects of lowering low-density lipoprotein cholesterol among 9,438 patients with chronic kidney disease

    NARCIS (Netherlands)

    Baigent, C.; Landray, M.; Reith, C.; Dasgupta, T.; Emberson, J.; Herrington, W.; Lewis, D.; Mafham, M.; Collins, R.; Collins, R.; Baigent, C.; Landray, M.; Bray, C.; Chen, Y.; Baxter, A.; Young, A.; Hill, M.; Knott, C.; Cass, A.; Feldt-Rasmussen, B.; Fellstroem, B.; Grobbee, R.; Groenhagen-Riska, C.; Haas, M.; Holdaas, H.; Hooi, L. S.; Jiang, L.; Kasiske, B.; Krairittichai, U.; Levin, A.; Massy, Z.; Tesar, V.; Walker, R.; Wanner, C.; Wheeler, D.; Wiecek, A.; Dasgupta, T.; Lewis, D.; Mafham, M.; Majoni, W.; Reith, C.; Simpson, D.; Strony, J.; Musliner, T.; Agodoa, L.; Armitage, J.; Chen, Z.; Craig, J.; de Zeeuw, D.; Gaziano, M.

    2010-01-01

    Background Lowering low-density lipoprotein (LDL) cholesterol with statin therapy has been shown to reduce the incidence of atherosclerotic events in many types of patient, but it remains uncertain whether it is of net benefit among people with chronic kidney disease (CKD). Methods Patients with

  4. Association between Low-density lipoprotein cholesterol and occipital periventricular hyperintensities in a group of Chinese patients: an observational study.

    Science.gov (United States)

    Duan, Dazhi; Shen, Lin; Cui, Chun; Shu, Tongsheng; Zheng, Jian

    2017-02-27

    While occipital periventricular hyperintensities (OPVHs) are among the most common mild white matter hyperintensities, the clinical factors associated with OPVHs remain unclear. In this study, we investigated the role of clinical factors in development of pure OPVHs. This study included 97 patients with OPVHs and 73 healthy controls. Univariate analysis of clinical factors in OPVH patients and controls was followed by binomial logistic regression analysis to identify clinical factors significantly associated with OPVHs. Univariate analysis indicated that age, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein-B (Apo-B) levels differed significantly between the OPVH patients and controls (p correlated with OPVH scores (p anti-correlated with OPVHs scores (p correlated with OPVHs (p correlated with OPVHs (p < 0.001). In summary, LDL-C was negatively and age was positively associated with OPVHs among Chinese patients in a hospital.

  5. Effect of cocoa bran on low-density lipoprotein oxidation and fecal bulking.

    Science.gov (United States)

    Jenkins, D J; Kendall, C W; Vuksan, V; Vidgen, E; Wong, E; Augustin, L S; Fulgoni, V

    Legumes have reported benefits in terms of reduced risk for coronary heart disease and of colonic health. A novel legume fiber, cocoa bran, also may have favorable health effects on serum lipid levels, low-density lipoprotein (LDL) cholesterol oxidation, and fecal bulk. Twenty-five healthy normolipidemic subjects (13 men and 12 women) (mean +/- SEM age, 37 +/- 2 years; mean +/- SEM body mass index [calculated as weight in kilograms divided by the square of height in meters], 24.6 +/- 0.7) ate cocoa-bran and chocolate-flavored low-fiber breakfast cereals for 2-week periods, with 2-week washout, in a double-blind crossover study. The cocoa-bran cereal provided 25.0 g/d of total dietary fiber (TDF). The low-fiber cereal (5.6 g/d TDF) was of similar appearance and energy value. Fasting blood samples were obtained at the start and end of each period, and 4-day fecal collections were made from days 11 through 14. High-density lipoprotein (HDL) cholesterol level was higher (7.6% +/- 2.9%; P =.02) and the LDL/HDL cholesterol ratio was lower (6.7% +/- 2.3%; P =.007) for cocoa-bran compared with low-fiber cereal at 2 weeks. No effect was seen on LDL cholesterol oxidation. Mean fecal output was significantly higher for cocoa-bran than for low-fiber cereal (56 +/- 14 g/d; Pchocolate-flavored cocoa-bran cereal increased fecal bulk similarly to wheat bran and was associated with a reduction in the LDL/HDL cholesterol ratio. In view of the low-fat, high-fiber nature of the material, these results suggest a possible role for this novel fiber source in the diets of normal, hyperlipidemic, and constipated subjects.

  6. Regulation of low density lipoprotein receptor function in a human hepatoma cell line

    International Nuclear Information System (INIS)

    Leichtner, A.M.; Krieger, M.; Schwartz, A.L.

    1984-01-01

    Low density lipoprotein (LDL) processing was investigated in a human hepatoma-derived cell line, Hep G2. Hep G2 cells bound, internalized and degraded LDL via a saturable, high affinity pathway similar to that present in other mammalian cells. Although 80% of the uptake and degradation of 125 I-LDL was inhibited by 40-fold excess native LDL, the same concentration of methylated LDL, which cannot bind to LDL receptors, had virtually no effect on processing. When added at low concentrations, the lysosomotropic agent, chloroquine, inhibited degradation without affecting the rate of lipoprotein internalization. Receptor activity was decreased 60% by preincubation of the cells in medium containing a source of cholesterol (LDL or unesterified cholesterol) and increased 1.7-fold by preincubation with compactin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. The Hep G2 cell line may prove a useful system both for the further study of hepatic lipoprotein metabolism and for the evaluation of new antihypercholesterolemic agents

  7. Characterization of blood lipoproteins and validation of cholesterol and triacylglycerol assays for free-ranging polar bears (Ursus maritimus).

    Science.gov (United States)

    Whiteman, John P; Frank, Nicholas; Greller, Katie A; Harlow, Henry J; Ben-David, Merav

    2013-05-01

    Blood triacylglycerol (TG) and lipoproteins are important variables for evaluating nutritional status of wildlife, but measurements are often expensive and difficult. Performance of a small, portable blood analyzer intended for human medical diagnostics was evaluated in measuring these variables in plasma and serum from free-ranging polar bears (Ursus maritimus), which are experiencing nutritional stress related to sea ice loss. The analyzer accurately tracked changes in concentration of total cholesterol (Ctotal), cholesterol associated with high-density lipoprotein (CHDL), and TG during a validation protocol of diluting samples and spiking them with exogenous cholesterol and glycerol. Values of Ctotal and TG agreed well with values obtained by other methods (ultracentrifugation followed by colorimetric assays); agreement was variable for values of cholesterol associated with specific lipoproteins. Similar to a study of captive polar bears, ultracentrifugation methods revealed greater TG in very low-density lipoproteins than in low-density lipoprotein, which is unusual and merits additional study.

  8. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management

    Science.gov (United States)

    Chapman, M. John; Ginsberg, Henry N.; Amarenco, Pierre; Andreotti, Felicita; Borén, Jan; Catapano, Alberico L.; Descamps, Olivier S.; Fisher, Edward; Kovanen, Petri T.; Kuivenhoven, Jan Albert; Lesnik, Philippe; Masana, Luis; Nordestgaard, Børge G.; Ray, Kausik K.; Reiner, Zeljko; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Tybjærg-Hansen, Anne; Watts, Gerald F.

    2011-01-01

    Even at low-density lipoprotein cholesterol (LDL-C) goal, patients with cardiometabolic abnormalities remain at high risk of cardiovascular events. This paper aims (i) to critically appraise evidence for elevated levels of triglyceride-rich lipoproteins (TRLs) and low levels of high-density lipoprotein cholesterol (HDL-C) as cardiovascular risk factors, and (ii) to advise on therapeutic strategies for management. Current evidence supports a causal association between elevated TRL and their remnants, low HDL-C, and cardiovascular risk. This interpretation is based on mechanistic and genetic studies for TRL and remnants, together with the epidemiological data suggestive of the association for circulating triglycerides and cardiovascular disease. For HDL, epidemiological, mechanistic, and clinical intervention data are consistent with the view that low HDL-C contributes to elevated cardiovascular risk; genetic evidence is unclear however, potentially reflecting the complexity of HDL metabolism. The Panel believes that therapeutic targeting of elevated triglycerides (≥1.7 mmol/L or 150 mg/dL), a marker of TRL and their remnants, and/or low HDL-C (<1.0 mmol/L or 40 mg/dL) may provide further benefit. The first step should be lifestyle interventions together with consideration of compliance with pharmacotherapy and secondary causes of dyslipidaemia. If inadequately corrected, adding niacin or a fibrate, or intensifying LDL-C lowering therapy may be considered. Treatment decisions regarding statin combination therapy should take into account relevant safety concerns, i.e. the risk of elevation of blood glucose, uric acid or liver enzymes with niacin, and myopathy, increased serum creatinine and cholelithiasis with fibrates. These recommendations will facilitate reduction in the substantial cardiovascular risk that persists in patients with cardiometabolic abnormalities at LDL-C goal. PMID:21531743

  9. Preferential enrichment of large-sized very low density lipoprotein populations with transferred cholesteryl esters

    International Nuclear Information System (INIS)

    Eisenberg, S.

    1985-01-01

    The effect of lipid transfer proteins on the exchange and transfer of cholesteryl esters from rat plasma HDL2 to human very low (VLDL) and low density (LDL) lipoprotein populations was studied. The use of a combination of radiochemical and chemical methods allowed separate assessment of [ 3 H]cholesteryl ester exchange and of cholesteryl ester transfer. VLDL-I was the preferred acceptor for transferred cholesteryl esters, followed by VLDL-II and VLDL-III. LDL did not acquire cholesteryl esters. The contribution of exchange of [ 3 H]cholesteryl esters to total transfer was highest for LDL and decreased in reverse order along the VLDL density range. Inactivation of lecithin: cholesterol acyltransferase (LCAT) and heating the HDL2 for 60 min at 56 degrees C accelerated transfer and exchange of [ 3 H]cholesteryl esters. Addition of lipid transfer proteins increased cholesterol esterification in all systems. The data demonstrate that large-sized, triglyceride-rich VLDL particles are preferred acceptors for transferred cholesteryl esters. It is suggested that enrichment of very low density lipoproteins with cholesteryl esters reflects the triglyceride content of the particles

  10. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    Science.gov (United States)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

  11. In vivo transfer of cholesteryl ester from high and low density plasma lipoproteins into human aortic tissue

    International Nuclear Information System (INIS)

    Stender, S.; Hjelms, E.

    1988-01-01

    For the study of cholesteryl ester transfer from different plasma lipoproteins into human aortic tissue, patients scheduled for reconstructive aortic surgery were intravenously injected with autologous in vitro labeled lipoproteins 20 to 24 hours before aortic intima-media samples were obtained during the operation. The injectate contained high density lipoproteins (d greater than 1.063) labeled with 3H-cholesteryl ester and lipoproteins of lower density (d less than 1.063) labeled with 14C-cholesteryl ester or lipoproteins with the opposite labeling. In 16 aortic tissue samples (some with visible atherosclerosis) from 11 normocholesterolemic patients, the aortic influx of total cholesteryl ester was 1 to 50 nmol x cm-2 x day-1. Some 39% +/- 3% (mean +/- SEM) of the influx was derived from high density lipoproteins, which in plasma accounted for only 22% +/- 2% (mean +/- SEM) of the esterified cholesterol. The findings suggest that: 1) esterified cholesterol from the two lipoprotein fractions in plasma enter the aortic intima by the same mechanism, and 2) influx of cholesteryl ester from the smaller, high density lipoproteins is greater than influx from the larger, lower density lipoproteins considering their concentrations in plasma. In some patients, the cholesterol content in the intima-media tissue with no visible atherosclerosis corresponded to only a few months of continuous cholesteryl ester influx. This time is short considering the age of the patients and, therefore, indicates that removal of esterified cholesterol from the intima-media is of major importance in preventing cholesterol deposition in the arterial wall

  12. Kandungan kolesterol, High Density Lipoprotein (HDL dan low density lipopro-tein (LDL darah burung puyuh dengan pemberian aditif cair buah naga merah

    Directory of Open Access Journals (Sweden)

    Khabib Arrosichin

    2016-04-01

    Full Text Available The study aims to determine, assess and evaluate the content of cholesterol, high density lipoprotein (HDL and Low Density Lipoprotein (LDL blood quail which were treated with liquid additive red dragon fruit. Materials used in the study were 200 female quails aged 14 days with an average weight of 13.61 ± 0.49 g. Ration composed by metabolizable energy content of ± 3000 kcal/kg and ± 20% of crude protein. The study consisted of 4 treatments and 5 replications. The treatments were (T0: without addition of liquid red dragon fruit (control; T1: addition of 5 ml liquid red dragon fruit twice a day; T2: addition of 5 ml liquid red dragon fruit once a day and T3: addition of 5 ml liquid red dragon fruit once in every two days. Blood sampling was performed in EDTA tube at the end of the study. Analysis of samples was carried out in health laboratory Semarang. The results were analyzed using analysis of variance (ANOVA. The study showed that the addition of liquid red dragon fruit additive had no significant effect (P> 0.05 on cholesterol, HDL and LDL of quil’s blood. Keywords: Quail, cholesterol; HDL, LDL, and red dragon fruit

  13. Gold nanocrystal labeling allows low-density lipoprotein imaging from the subcellular to macroscopic level

    NARCIS (Netherlands)

    Allijn, Iris E.; Leong, Wei; Tang, Jun; Gianella, Anita; Mieszawska, Aneta J.; Fay, Francois; Ma, Ge; Russell, Stewart; Callo, Catherine B.; Gordon, Ronald E.; Korkmaz, Emine; Post, Jan Andries; Zhao, Yiming; Gerritsen, Hans C.; Thran, Axel; Proksa, Roland; Daerr, Heiner; Storm, Gert; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.; Cormode, David P.

    2013-01-01

    Low-density lipoprotein (LDL) plays a critical role in cholesterol transport and is closely linked to the progression of several diseases. This motivates the development of methods to study LDL behavior from the microscopic to whole-body level. We have developed an approach to efficiently load LDL

  14. Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol

    DEFF Research Database (Denmark)

    Feitosa, Mary F; Wojczynski, Mary K; Straka, Robert

    2014-01-01

    The plasma levels of high-density lipoprotein cholesterol (HDL) have an inverse relationship to the risks of atherosclerosis and cardiovascular disease (CVD), and have also been associated with longevity. We sought to identify novel loci for HDL that could potentially provide new insights...

  15. Use of 3H-colesterol and its kinetics to assess the dynamics of the cholesterol metabolism in human lipoprotein fractions

    International Nuclear Information System (INIS)

    Grossmann, K.D.; Marek, H.; Fieber, R.S.

    1982-01-01

    The assessment of the dynamics of 3 H cholesterols in very low, low and high density lipoproteins, resp. lipoproteins after oral administration in normal subjects and in patients with hyperlipoproteinemia type II a and II b is described. Specific activity-time-curves of the lipoprotein fractions isolated by means of discontinuous ultracentrifugation were recorded. In order to optimize the centrifugation activity-electrophoresis-profiles of the separating steps were recorded. The fractions obtained were characterized by the determination of cholesterol, agarose electrophoresis and radioactivity measurement. The turnover of the tracer in the lipoproteins was determined on the basis of the maximum values of the specific activity-time-curves. Hyperlipoproteinemia patients showed time shifts of the maximum values especially with regard to esterized cholesterols and high density lipoprotein cholesterol as compared to healthy persons. (author)

  16. Acrolein impairs the cholesterol transport functions of high density lipoproteins.

    Science.gov (United States)

    Chadwick, Alexandra C; Holme, Rebecca L; Chen, Yiliang; Thomas, Michael J; Sorci-Thomas, Mary G; Silverstein, Roy L; Pritchard, Kirkwood A; Sahoo, Daisy

    2015-01-01

    High density lipoproteins (HDL) are considered athero-protective, primarily due to their role in reverse cholesterol transport, where they transport cholesterol from peripheral tissues to the liver for excretion. The current study was designed to determine the impact of HDL modification by acrolein, a highly reactive aldehyde found in high abundance in cigarette smoke, on the cholesterol transport functions of HDL. HDL was chemically-modified with acrolein and immunoblot and mass spectrometry analyses confirmed apolipoprotein crosslinking, as well as acrolein adducts on apolipoproteins A-I and A-II. The ability of acrolein-modified HDL (acro-HDL) to serve as an acceptor of free cholesterol (FC) from COS-7 cells transiently expressing SR-BI was significantly decreased. Further, in contrast to native HDL, acro-HDL promotes higher neutral lipid accumulation in murine macrophages as judged by Oil Red O staining. The ability of acro-HDL to mediate efficient selective uptake of HDL-cholesteryl esters (CE) into SR-BI-expressing cells was reduced compared to native HDL. Together, the findings from our studies suggest that acrolein modification of HDL produces a dysfunctional particle that may ultimately promote atherogenesis by impairing functions that are critical in the reverse cholesterol transport pathway.

  17. In vitro incorporation of radiolabeled cholesteryl esters into high and low density lipoproteins

    International Nuclear Information System (INIS)

    Terpstra, A.H.; Nicolosi, R.J.; Herbert, P.N.

    1989-01-01

    We have developed and validated a method for in vitro incorporation of radiolabeled cholesteryl esters into low density (LDL) and high density lipoproteins (HDL). Radiolabeled cholesteryl esters dissolved in absolute ethanol were mixed with LDL or HDL in the presence of lipoprotein-deficient serum (LPDS) as a source of core lipid transfer activity. The efficiency of incorporation was dependent on: (a) the core lipid transfer activity and quantity of LPDS, (b) the mass of added radiolabeled cholesteryl esters, (c) the length of incubation, and (d) the amount of acceptor lipoprotein cholesterol. The tracer incorporation was documented by repeat density gradient ultracentrifugation, agarose gel electrophoresis, and precipitation with heparin-MnCl2. The radiolabeling conditions did not affect the following properties of the lipoproteins: (1) chemical composition, (2) electrophoretic mobility on agarose gels, (3) hydrated density, (4) distribution of apoproteins on SDS gels, (5) plasma clearance rates, and (6) immunoprecipitability of HDL apoproteins A-I and A-II. Rat HDL containing radiolabeled cholesteryl esters incorporated in vitro had plasma disappearance rates identical to HDL radiolabeled in vivo

  18. Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

    Science.gov (United States)

    Oda, Hitomi; Mori, Akihiro; Hirowatari, Yuji; Takoura, Toshie; Manita, Daisuke; Takahashi, Tomoya; Shono, Saori; Onozawa, Eri; Mizutani, Hisashi; Miki, Yohei; Itabashi, Yukiko; Sako, Toshinori

    2017-10-01

    Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

    Science.gov (United States)

    Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

    2017-03-01

    Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

  20. High Density Lipoprotein and it's Dysfunction.

    Science.gov (United States)

    Eren, Esin; Yilmaz, Necat; Aydin, Ozgur

    2012-01-01

    Plasma high-density lipoprotein cholesterol(HDL-C) levels do not predict functionality and composition of high-density lipoprotein(HDL). Traditionally, keeping levels of low-density lipoprotein cholesterol(LDL-C) down and HDL-C up have been the goal of patients to prevent atherosclerosis that can lead to coronary vascular disease(CVD). People think about the HDL present in their cholesterol test, but not about its functional capability. Up to 65% of cardiovascular death cannot be prevented by putative LDL-C lowering agents. It well explains the strong interest in HDL increasing strategies. However, recent studies have questioned the good in using drugs to increase level of HDL. While raising HDL is a theoretically attractive target, the optimal approach remains uncertain. The attention has turned to the quality, rather than the quantity, of HDL-C. An alternative to elevations in HDL involves strategies to enhance HDL functionality. The situation poses an opportunity for clinical chemists to take the lead in the development and validation of such biomarkers. The best known function of HDL is the capacity to promote cellular cholesterol efflux from peripheral cells and deliver cholesterol to the liver for excretion, thereby playing a key role in reverse cholesterol transport (RCT). The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High antioxidant and anti-inflammatory activities of HDL are associated with protection from CVD.This review addresses the current state of knowledge regarding assays of HDL functions and their relationship to CVD. HDL as a therapeutic target is the new frontier with huge potential for positive public health implications.

  1. Density profile and cholesterol concentration of serum lipoproteins in experimental animals and human subjects on hypercholesterolaemic diets

    NARCIS (Netherlands)

    Beynen, A.C.; Terpstra, A.H.M.

    1984-01-01

    1. 1. The density profile of Sudan black stained serum lipoproteins was studied in human subjects and various animal species on diets supplemented with cholesterol. 2. 2. In the animals studied (rabbits, calves, mice, chickens, rats and guinea-pigs), the feeding of cholesterol resulted in an

  2. The Influence of Decreased Levels of High Density Lipoprotein ...

    African Journals Online (AJOL)

    Background: Changes in lipoproteins levels in sickle cell disease (SCD) patients are well.known, but the physiological ramifications of the low levels observed have not been entirely resolved. Aim: The aim of this study is to evaluate the impact of decreased levels of high density lipoprotein cholesterol (HDL.c) on ...

  3. Effect of the Probiotic Saccharomyces boulardii on Cholesterol and Lipoprotein Particles in Hypercholesterolemic Adults: A Single-Arm, Open-Label Pilot Study.

    Science.gov (United States)

    Ryan, Jennifer Joan; Hanes, Douglas Allen; Schafer, Morgan Beth; Mikolai, Jeremy; Zwickey, Heather

    2015-05-01

    Elevated blood cholesterol levels are a major risk factor for coronary artery disease, the leading cause of death worldwide. Probiotics have been investigated as potential cholesterol-lowering therapies, but no previous studies have assessed the effect of the probiotic yeast Saccharomyces boulardii on cholesterol levels in human volunteers. The objective of this study was to examine the effect of S. boulardii on serum cholesterol and lipoprotein particles in hypercholesterolemic adults. This study was a single-arm, open-label pilot study. Twelve hypercholesterolemic participants were recruited into the study; one dropped out. Participants took 5.6×10(10) colony forming unit (CFU) encapsulated S. boulardii (Saccharomyces cerevisiae var. boulardii CNCM I-1079) twice daily for an 8-week period. Fasting concentrations of cholesterol (total cholesterol, low-density lipoprotein-cholesterol [LDL-C], high-density lipoprotein-cholesterol [HDL-C], and triglycerides), lipoprotein particles (very-low-density lipoprotein-particle [VLDL-P], remnant lipoprotein particle [RLP-P], total LDL-P, LDL III-P, LDL IV-P, total HDL-P, and HDL 2b-P), and additional cardiovascular biomarkers (apo B-100, lipoprotein [a], high-sensitivity C-reactive protein, homocysteine, fibrinogen, and insulin) were measured at baseline, after 4 weeks, and after 8 weeks. Remnant lipoprotein particles decreased by 15.5% (p=0.03) over the 8-week period. The remaining outcome measures were not significantly altered. In this pilot study, 8 weeks of daily supplementation with S. boulardii lowered remnant lipoprotein, a predictive biomarker and potential therapeutic target in the treatment and prevention of coronary artery disease.

  4. Metabolism of high density lipoproteins reconstituted with [3H]cholesteryl ester and [14C]cholesterol in the rat, with special reference to the ovary

    International Nuclear Information System (INIS)

    Nestler, J.E.; Bamberger, M.; Rothblat, G.H.; Strauss, J.F. III

    1985-01-01

    In order to study the metabolism of high density lipoprotein (HDL)-carried sterol in the rat, human HDL was reconstituted with [ 14 C]cholesterol and [ 3 H]cholesteryl ester. After iv injection into immature PMSG-human CG primed rats pretreated with 4-aminopyrazolopyrimidine and aminoglutethimide, there was time-dependent accumulation of 3 H and 14 C in various organs which reached a maximum by 15-90 min. On a milligram wet weight basis, uptake of 3 H and 14 C was greatest in the adrenals, next in ovaries, followed by the liver, with little uptake by kidneys and spleen. On an organ basis, accumulation was greatest by the liver. Coadministration of excess unlabeled HDL, but not human low density lipoprotein, reduced accumulation of radioactivity by the ovaries and adrenals by 60%, indicating a specific and saturable uptake process. Granulosa cells cultured in lipoprotein-deficient medium with reconstituted HDL formed 3 H- and 14 C-labeled 20 alpha-hydroxypregn-4-en-3-one. Over a 24-h period, utilization of both [ 14 C]cholesterol and [ 3 H]cholesteryl ester was linear, but rates of utilization of the two sterol moieties were not parallel. Lysosomotropic agents had no effect on utilization of either free or esterified cholesterol for steroidogenesis but reduced degradation of 125 I-labeled low density lipoprotein apoprotein. These findings lend further support to the concept of a distinct HDL pathway in steroidogenic cells of the rat

  5. Contemporary data on treatment practices for low-density lipoprotein cholesterol in 3867 patients who had suffered an acute coronary syndrome across the world

    Directory of Open Access Journals (Sweden)

    Anselm K. Gitt

    2018-02-01

    Full Text Available DYSIS II ACS was a longitudinal, observational study in 3867 patients from 18 countries. They were being hospitalized after suffering an acute coronary syndrome. Evaluations were performed at the time of admission and again 120±15 days following the date of admission (the follow-up time point. 2521 patients were on active lipid lowering treatment (LLT at admission. Mean atorvastatin dose was 22 mg per day and 2.7% received ezetimibe in combination with a statin. At discharge from hospital, 3767 patients received LLT expressed as a mean atorvastatin dose of 36 mg per day with 4.8% receiving ezetimibe on top of a statin. After 120 days, intensity in lipid lowering treatment was reduced to 32 mg per day with 4.9% of the patients receiving ezetimibe and a statin. Of note, during this 4-month follow up period, only 32% of all patients received laboratory lipid testing. 37% attained the low density lipoprotein cholesterol (LDL-C target value of <70 mg/dl after 120 days. There are differences in the therapy administered as well as in the switch strategies when comparing the data from the respective countries studied. Conclusions: Only one in three patients achieved the LDL-C target value following only marginal improvements in atorvastatin dose or combination therapy after an ACS event. Keywords: Low-density lipoprotein cholesterol, Treatment target, Global, Region, Statins

  6. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, Adam R. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Rachel L. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G.; Larson, Richard; Li, Li [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Masuda, Hiroko; Brewer, Takae [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Atkinson, Bradley J. [Department of Clinical Pharmacy Services, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Brewster, Abeena [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Department of Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2015-04-01

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  7. High-Density and Very-Low-Density Lipoprotein Have Opposing Roles in Regulating Tumor-Initiating Cells and Sensitivity to Radiation in Inflammatory Breast Cancer

    International Nuclear Information System (INIS)

    Wolfe, Adam R.; Atkinson, Rachel L.; Reddy, Jay P.; Debeb, Bisrat G.; Larson, Richard; Li, Li; Masuda, Hiroko; Brewer, Takae; Atkinson, Bradley J.; Brewster, Abeena; Ueno, Naoto T.; Woodward, Wendy A.

    2015-01-01

    Purpose: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. Methods and Materials: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. Results: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). Conclusions: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients

  8. Adrenal imaging with technetium-99m-labelled low density lipoproteins

    International Nuclear Information System (INIS)

    Isaacsohn, J.L.; Lees, A.M.; Lees, R.S.; Strauss, H.W.; Barlai-Kovach, M.; Moore, T.J.

    1986-01-01

    Evaluation of adrenal cortical function by external imaging is currently accomplished by injection of radiolabelled analogs of cholesterol. Although the adrenals do utilized exogenous cholesterol for steroid hormone synthesis, the cholesterol is delivered to the glands not as free cholesterol but through the uptake of low density lipoproteins (LDL), which are subsequently degraded within the adrenal cortical cells to provide cholesterol. Thus, we sought to assess the use of /sup 99m/Tc-labelled LDL injected into rabbits to obtain external images of the adrenal glands. Adrenal images of all nine rabbits tested were obtained within 18 to 21 hours after injection of /sup 99m/Tc-LDL. Seven of the rabbits were subjected to adrenal cortical suppression with dexamethasone and then all nine rabbits were imaged a second time. In the untreated animals, visualization of the adrenal glands was accompanied by normal serum cortisol concentrations and accumulation of radiolabel in the adrenals, whereas in the dexamethasone-treated animals, lack of visualization of the adrenal glands was correlated with low serum cortisols, and greatly decreased accumulation of the radionuclide in the adrenals. These findings demonstrate for the first time that LDL, when labelled with /sup 99m/Tc, can be used to evaluate adrenal cortical function by external imaging

  9. Levels of high-density lipoprotein cholesterol (HDL-C among children with steady-state sickle cell disease

    Directory of Open Access Journals (Sweden)

    Seixas Magda O

    2010-08-01

    Full Text Available Abstract Background The search for sickle cell disease (SCD prognosis biomarkers is a challenge. These markers identification can help to establish further therapy, later severe clinical complications and with patients follow-up. We attempted to study a possible involvement of levels of high-density lipoprotein cholesterol (HDL-C in steady-state children with SCD, once that this lipid marker has been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities, important aspects to be considered in sickle cell disease pathogenesis. Methods We prospectively analyzed biochemical, inflammatory and hematological biomarkers of 152 steady-state infants with SCD and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Results Of the 152 infants investigated had a significant positive association of high-density lipoprotein cholesterol with hemoglobin (P Conclusions We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by low HDL-C with hypertriglyceridemia and high VLDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. Additional studies are warranted to test this hypothesis and the probably mechanisms involved in this complex network of markers and their role in SCD pathogenesis.

  10. Impact of hydrogenated fat consumption on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein to oxidation in moderately hypercholesterolemic individuals.

    Science.gov (United States)

    Cuchel, M; Schwab, U S; Jones, P J; Vogel, S; Lammi-Keefe, C; Li, Z; Ordovas, J; McNamara, J R; Schaefer, E J; Lichtenstein, A H

    1996-02-01

    The effects of replacing corn oil with corn oil margarine in stick form on endogenous cholesterol synthesis and susceptibility of low-density lipoprotein (LDL) to oxidation were assessed in 14 middle-aged and elderly men and women aged 63 +/- 12 years (mean +/- SD) with moderate hypercholesterolemia (mean LDL-cholesterol [LDL-C], 4.24 +/- 0.59 mmol/L at the time of recruitment). Subjects consumed each of two diets for 32-day periods, one enriched in corn oil, which contained 30% of energy as fat (7% saturated fatty acid [SFA], 9% monounsaturated fatty acid [MUFA] [0.4% 18:1n9 trans], and 11% polyunsaturated fatty acid [PUFA]) and 85 mg cholesterol/4.2 MJ, and one enriched in stick corn oil margarine, which contained 30% fat (8% SFA, 12% MUFA [4.2% 18:1n9trans], and 8% PUFA) and 77 mg cholesterol/4.2 MJ. Both diets were isocaloric and supplied by a metabolic research kitchen. Mean total cholesterol levels were lowest (P = .039) when subjects consumed the corn oil-enriched diet (5.01 +/- 0.51 mmol/L) as compared with the margarine-enriched diet (5.30 +/- 0.58 mmol/L). LDL-C levels were 3.24 +/- 0.51 and 3.50 +/- 0.54 mmol/L when subjects consumed corn oil-and margarine-enriched diets, respectively (P = .058). There were no significant differences in high-density lipoprotein cholesterol (HDL-C) or triglyceride concentrations between the two experimental periods. Consumption of the margarine-enriched diet versus the corn oil-enriched diet tended to result in lower cholesterol fractional synthetic rates ([C-FSRs] 0.0466 +/- 0.0175 and 0.0668 +/- 0.0298, respectively, P = .080) and cholesterol absolute synthetic rates ([C-ASRs] 1.1761 +/- 0.5375 and 1.6954 +/- 0.8685, respectively, P = .092); however, differences did not reach statistical significance. Consumption of the margarine-enriched diet versus the corn oil-enriched diet resulted in a significantly higher concentration of alpha-tocopherol in both plasma and LDL(P = .004 and P = .011, respectively). LDL particle

  11. Measurement of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins

    International Nuclear Information System (INIS)

    Karlin, J.B.; Juhn, D.J.; Fless, G.; Scanu, A.M.; Rubenstein, A.H.

    1978-01-01

    A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The antiserum was raised to LDL (d 1.030 to 1.040 g/ml) and the LDL 2 (d 1.020 to 1.050 g/ml) was labeled with 125 I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02 to 0.5 μg of LDL 2 , had an interassay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an average American diet, a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet

  12. Accumulation of Oxidized Low-Density Lipoprotein in Psoriatic Skin and Changes of Plasma Lipid Levels in Psoriatic Patients

    Directory of Open Access Journals (Sweden)

    Nilgun Solak Tekin

    2007-01-01

    Full Text Available Background. Psoriasis is a chronic inflammatory skin disease characterized by an accelerated turnover of epidermal cells and an incomplete differentiation in epidermis with lesion. However, the exact etiology of psoriasis is unknown. Abnormalities in essential fatty acid metabolism, free radical generation, lipid peroxidation, and release of lymphokines have been proposed. Objective. Our purpose was to evaluate the plasma lipids and oxidized low-density lipoprotein accumulation in psoriatic skin lesion in order to ascertain the possible participation of oxidative stress and oxidative modification of lipids in pathogenesis of psoriasis. Methods. The study group included 84 patients with psoriasis, and 40 sex- and age-matched healthy volunteers. Blood lipid profile was determined. Psoriatic and nonlesional skin samples of psoriatic patients were evaluated for the presence of oxidized low-density lipoprotein by using an immune-fluorescent staining method. Results. The mean levels of lipids (total cholesterol, triglyceride, and LDL cholesterol in patients with psoriasis were found to be significantly higher than those of healthy subjects. Psoriatic skins were shown positive oxidized low-density lipoprotein staining. There was no staining in nonlesional skin samples of the same individuals. Conclusion. Lipid peroxidation mediated by free radicals is believed to be one of the important causes of cell membrane destruction and cell damage. This study shows for the first time the accumulation of oxidized low-density lipoprotein in psoriatic skin lesion. We believe that accumulation of ox-LDL in psoriatic skin may have an important role in the immune-inflammatory events that result in progressive skin damage.

  13. Interfacial Tension and Surface Pressure of High Density Lipoprotein, Low Density Lipoprotein, and Related Lipid Droplets

    DEFF Research Database (Denmark)

    Ollila, O. H. S.; Lamberg, A.; Lehtivaara, M.

    2012-01-01

    ) are essentially lipid droplets surrounded by specific proteins, their main function being to transport cholesterol. Interfacial tension and surface pressure of these particles are of great interest because they are related to the shape and the stability of the droplets and to protein adsorption at the interface....... Here we use coarse-grained molecular-dynamics simulations to consider a number of related issues by calculating the interfacial tension in protein-free lipid droplets, and in HDL and LDL particles mimicking physiological conditions. First, our results suggest that the curvature dependence......Lipid droplets play a central role in energy storage and metabolism on a cellular scale. Their core is comprised of hydrophobic lipids covered by a surface region consisting of amphiphilic lipids and proteins. For example, high and low density lipoproteins (HDL and LDL, respectively...

  14. Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients

    Directory of Open Access Journals (Sweden)

    Cal Roi

    2012-08-01

    Full Text Available Abstract Our hypothesis was that overexpression of certain lipoprotein receptors might be related to lipid accumulation in the human ischemic myocardium. Intramyocardial lipid overload contributes to contractile dysfunction and arrhythmias in cardiomyopathy. Thus, the purpose of this study was to assess the effect of hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in cardiomyocytes, as well as the potential correlation between LRP1 expression and neutral lipid accumulation in the left ventricle tissue from ischemic cardiomyopathy patients. Cell culture experiments include control and LRP1-deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts (CNT were included. Low density lipoprotein receptor-related protein 1 (LRP1, very low density lipoprotein receptor (VLDLR and low density lipoprotein receptor (LDLR expression was analyzed by real time PCR and Western blotting. Cholesteryl ester (CE, triglyceride (TG and free cholesterol (FC content was assess by thin layer chromatography following lipid extraction. Western blotting experiments showed that protein levels of LRP1, VLDLR and HIF-1α were significantly upregulated in ischemic hearts. Immunohistochemistry and confocal microscopy analysis showed that LRP1 and HIF-1α were upregulated in cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes. Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic hearts. Taken together, our results suggest that LRP1 upregulation is key for myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1 may be a target to prevent the deleterious effects of myocardial cholesterol accumulation in ischemic cardiomyopathy.

  15. In vitro production of beta-very low density lipoproteins and small, dense low density lipoproteins in mildly hypertriglyceridemic plasma: role of activities of lecithin:cholester acyltransferase, cholesterylester transfer proteins and lipoprotein lipase.

    Science.gov (United States)

    Chung, B H; Segrest, J P; Franklin, F

    1998-12-01

    As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced

  16. Novel Therapies Focused on the High-Density Lipoprotein Particle

    NARCIS (Netherlands)

    van Capelleveen, Julian C.; Brewer, H. Bryan; Kastelein, John J. P.; Hovingh, G. Kees

    2014-01-01

    Cardiovascular disease (CVD) remains a major burden for morbidity and mortality in the general population, despite current efficacious low-density lipoprotein-cholesterol-lowering therapies. Consequently, novel therapies are required to reduce this residual risk. Prospective epidemiological studies

  17. Meta-regression analysis of the effect of trans fatty acids on low-density lipoprotein cholesterol.

    Science.gov (United States)

    Allen, Bruce C; Vincent, Melissa J; Liska, DeAnn; Haber, Lynne T

    2016-12-01

    We conducted a meta-regression of controlled clinical trial data to investigate quantitatively the relationship between dietary intake of industrial trans fatty acids (iTFA) and increased low-density lipoprotein cholesterol (LDL-C). Previous regression analyses included insufficient data to determine the nature of the dose response in the low-dose region and have nonetheless assumed a linear relationship between iTFA intake and LDL-C levels. This work contributes to the previous work by 1) including additional studies examining low-dose intake (identified using an evidence mapping procedure); 2) investigating a range of curve shapes, including both linear and nonlinear models; and 3) using Bayesian meta-regression to combine results across trials. We found that, contrary to previous assumptions, the linear model does not acceptably fit the data, while the nonlinear, S-shaped Hill model fits the data well. Based on a conservative estimate of the degree of intra-individual variability in LDL-C (0.1 mmoL/L), as an estimate of a change in LDL-C that is not adverse, a change in iTFA intake of 2.2% of energy intake (%en) (corresponding to a total iTFA intake of 2.2-2.9%en) does not cause adverse effects on LDL-C. The iTFA intake associated with this change in LDL-C is substantially higher than the average iTFA intake (0.5%en). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Lipoprotein Lipase and PPAR Alpha Gene Polymorphisms, Increased Very-Low-Density Lipoprotein Levels, and Decreased High-Density Lipoprotein Levels as Risk Markers for the Development of Visceral Leishmaniasis by Leishmania infantum

    Directory of Open Access Journals (Sweden)

    Márcia Dias Teixeira Carvalho

    2014-01-01

    Full Text Available In visceral leishmaniasis (VL endemic areas, a minority of infected individuals progress to disease since most of them develop protective immunity. Therefore, we investigated the risk markers of VL within nonimmune sector. Analyzing infected symptomatic and, asymptomatic, and noninfected individuals, VL patients presented with reduced high-density lipoprotein cholesterol (HDL-C, elevated triacylglycerol (TAG, and elevated very-low-density lipoprotein cholesterol (VLDL-C levels. A polymorphism analysis of the lipoprotein lipase (LPL gene using HindIII restriction digestion (N = 156 samples (H+ = the presence and H− = the absence of mutation revealed an increased adjusted odds ratio (OR of VL versus noninfected individuals when the H+/H+ was compared with the H−/H− genotype (OR = 21.3; 95% CI = 2.32–3335.3; P = 0.003. The H+/H+ genotype and the H+ allele were associated with elevated VLDL-C and TAG levels (P < 0.05 and reduced HDL-C levels (P < 0.05. An analysis of the L162V polymorphism in the peroxisome proliferator-activated receptor alpha (PPARα gene (n = 248 revealed an increased adjusted OR when the Leu/Val was compared with the Leu/Leu genotype (OR = 8.77; 95% CI = 1.41–78.70; P = 0.014. High TAG (P = 0.021 and VLDL-C (P = 0.023 levels were associated with susceptibility to VL, whereas low HDL (P = 0.006 levels with resistance to infection. The mutated LPL and the PPARα Leu/Val genotypes may be considered risk markers for the development of VL.

  19. Radiochemical and immunohistochemical detection of low density lipoprotein surface binding by lymphocytes

    International Nuclear Information System (INIS)

    Melzner, I.; Hambitzer, R.; Haferkamp, O.

    1983-01-01

    Human peripheral blood lymphocytes bind and take up low density lipoprotein (LDL) by receptor-mediated endocytosis. The binding of LDL was determiend by incubation with 125 I-LDL and an immunohistochemical assay. By both techniques a diminished rate of binding was found when cells were freshly isolated from the blood, but increased 5 to 10 fold when lymphocytes were incubated in lipoprotein-deficient medium for 72 hours. In addition, it was shown immunohistochemically that only few ceels showed an LDL-dependent fluorescent labelling: approximately 5 to 10 % of the freshly isolated lymphocytes and 40 to 50 % of the cells incubated for 72 hours under lipoprotein-free conditions. The present data indicate that not only the high affinity LDL receptor described by Goldstein and Braun may be involved in the uptake of cholesterol by lymphocytes, but also other binding sites, which may have immunological function in some lymphocyte subpopulations. (author)

  20. Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects.

    Science.gov (United States)

    Guay, Valérie; Lamarche, Benoît; Charest, Amélie; Tremblay, André J; Couture, Patrick

    2012-01-01

    High-fat, low-carbohydrate diets have been shown to raise plasma cholesterol levels, an effect associated with the formation of large low-density lipoprotein (LDL) particles. However, the impact of dietary intervention on time-course changes in LDL particle size has not been investigated. To test whether a short-term dietary intervention affects LDL particle size, we conducted a randomized, double-blind, crossover study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: high-fat diet (37% energy from fat and 50% from carbohydrates) and low-fat diet (25% energy from fat and 62% from carbohydrates). Plasma lipid levels and LDL particle size were assessed on fasting blood samples after 3 days of feeding on each diet. The LDL particles were characterized by polyacrylamide gradient gel electrophoresis. Compared with the low-fat diet, plasma cholesterol, LDL cholesterol, and high-density lipoprotein cholesterol were significantly increased (4.45 vs 4.78 mmol/L, P = .04; 2.48 vs 2.90 mmol/L, P = .005; and 1.29 vs 1.41 mmol/L, P = .005, respectively) following the 3-day high-fat diet. Plasma triglycerides and fasting apolipoprotein B-48 levels were significantly decreased after the high-fat diet compared with the low-fat diet (1.48 vs 1.01 mmol/L, P = .0003 and 9.6 vs 5.5 mg/L, P = .008, respectively). The high-fat diet was also associated with a significant increase in LDL particle size (255.0 vs 255.9 Å;P = .01) and a significant decrease in the proportion of small LDL particle (vs 44.6%, P = .01). As compared with a low-fat diet, the cholesterol-raising effect of a high-fat diet is associated with the formation of large LDL particles after only 3 days of feeding. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Activated platelets contribute to oxidized low-density lipoproteins and dysfunctional high-density lipoproteins through a phospholipase A2-dependent mechanism

    NARCIS (Netherlands)

    Blache, Denis; Gautier, Thomas; Tietge, Uwe J. F.; Lagrost, Laurent

    Plasma activity of secretory phospholipase A2 (sPLA2) increases in patients with cardiovascular disease. The present study investigated whether platelet-released sPLA2 induces low-density lipoprotein (LDL) and high-density lipoprotein (HDL) modifications that translate into changes in lipoprotein

  2. Oxidized low-density lipoprotein in postmenopausal women

    DEFF Research Database (Denmark)

    Jankowski, Vera; Just, Alexander R; Pfeilschifter, Johannes

    2014-01-01

    BACKGROUND: Oxidized low-density lipoprotein (oxLDL) leads to atherosclerosis and cardiovascular disease, the most frequent causes of death worldwide. After menopause, lipid and lipoprotein metabolism changes and women are at greater risk of cardiovascular disease compared to fertile women. The aim.......10-0.43). Although intima-media thickness did not differ, postmenopausal women with serous oxLDL had more often atherosclerotic plaques compared to women without oxLDL (6/66 vs. 0/467; P lipoprotein, impaired glucose intolerance, and DBP were independently associated...... with the occurrence of oxLDL. If oxLDL was present, higher high-density lipoprotein and glucose intolerance were associated with higher concentrations of oxLDL. In contrast, higher blood urea concentrations were associated with lower concentrations of oxLDL. CONCLUSION: This study presents the prevalence...

  3. Effect of phospholipase A treatment of low density lipoproteins on the dextran sulfate--lipoprotein interaction.

    Science.gov (United States)

    Nishida, T

    1968-09-01

    The effect of phospholipase A on the interaction of low density lipoproteins of the S(f) 0-10 class with dextran sulfate was studied in phosphate buffer of pH 7.4, ionic strength 0.1, by chemical, spectrophotometric, and centrifugal methods. When low density lipoproteins that had been treated with phospholipase A were substituted for untreated lipoproteins, the amount of insoluble dextran sulfate-lipoprotein complex formed was greatly reduced. Hydrolysis of over 20% of the lecithin and phosphatidyl ethanolamine constituents of the lipoproteins prevented the formation of insoluble complex. However, even the lipoproteins in which almost all the phosphoglycerides were hydrolyzed produced soluble complex, which was converted to insoluble complex upon addition of magnesium sulfate. It is apparent that the lipoproteins altered extensively by treatment with phospholipase A retain many characteristic properties of native low density lipoproteins. Fatty acids, but not lysolecithin, released by the action of phospholipase A interfered with the formation of insoluble complex; this interference was due to association of the fatty acids with the lipoproteins. With increases in the concentration of the associated fatty acids, the amounts of magnesium ion required for the conversion of soluble complex to insoluble complex increased progressively. Charge interaction is evidently of paramount importance in the formation of sulfated polysaccharide-lipoprotein complexes.

  4. High-density lipoproteins and adrenal steroidogenesis : A population-based study

    NARCIS (Netherlands)

    Buitenwerf, Edward; Kerstens, Michiel N.; Links, Thera P.; Kema, Ido P.; Dullaart, Robin P. F.

    BACKGROUND: Cholesterol trafficked within plasma lipoproteins, in particular high-density lipoproteins (HDL), may represent an important source of cholesterol that is required for adrenal steroidogenesis. Based on a urinary gas chromatography method, compromised adrenal function has been suggested

  5. Importance of high-density lipoprotein cholesterol levels in elderly diabetic individuals with type IIb dyslipidemia: A 2-year survey of cardiovascular events.

    Science.gov (United States)

    Ina, Koichiro; Hayashi, Toshio; Araki, Atsushi; Kawashima, Seinosuke; Sone, Hirohito; Watanabe, Hiroshi; Ohrui, Takashi; Yokote, Koutaro; Takemoto, Minoru; Kubota, Kiyoshi; Noda, Mitsuhiko; Noto, Hiroshi; Ding, Qun-Fang; Zhang, Jie; Yu, Ze-Yun; Yoon, Byung-Koo; Nomura, Hideki; Kuzuya, Masafumi

    2014-10-01

    The risk factors for ischemic heart disease (IHD) or cerebrovascular accident (CVA) in elderly diabetic individuals with type IIb dyslipidemia are not fully known. Therefore, we investigated the relationship between lipid levels and IHD and CVA in diabetic individuals with type IIb dyslipidemia. The Japan Cholesterol and Diabetes Mellitus Study is a prospective cohort study of 4014 type 2 diabetic patients (1936 women; age 67.4 ± 9.5 years). The primary end-points were the onset of IHD or CVA. Lipid and glucose levels, and other factors were investigated in relation to the occurrence of IHD or CVA. A total of 462 participants were included in the group of patients with type IIb dyslipidemia. The 462 diabetic participants with type IIb dyslipidemia were divided into those who were aged 75 years (n=168, 190 and 104, respectively). High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol/HDL-C were significantly associated with the risk of cardiovascular events in diabetic individuals with type IIb dyslipidemia who were aged dyslipidemia who were aged dyslipidemia who were aged <75 years. © 2013 Japan Geriatrics Society.

  6. Estimations of cholesterol, triglycerides and fractionation of lipoproteins in serum samples of some Nigerian female subjects

    Directory of Open Access Journals (Sweden)

    E.I. Adeyeye

    2011-04-01

    Full Text Available Blood samples (serum were collected to determine some biochemical parameters: total glycerides (TG, total cholesterol (TC, high density lipoprotein-cholesterol (HDL-C, low density lipoprotein-cholesterol (LDL-C and very low density lipoprotein-cholesterol (VLDL-C in 53 female subjects in Warri, Delta State, Nigeria using the Reflotron® (an auto analyser, supported with the use of questionnaire to get information on age and sex. Age range of the subjects was 18–80 years. The TG levels in all the subjects were < 200 mg/dL; only one subject (1.89% had TC < 200 mg/dL; nine subjects (17.0% had HDL-C ≤ 35 mg/dL; for LDL-C only one subject (1.89% had a desirable level of < 130 mg/dL; for VLDL-C 29 subjects (54.7% had values 17.2 mg/dL and above. For therapeutic decision-making, TC/HDL-C and LDL-C/HDL-C, were calculated. In TC/HDL-C, three subjects (5.66% had values < 4.4 and in LDL-C/HDL-C, 41 subjects (77.4% had values < 4.5. Hence, TC, HDL-C, LDL-C, TC/HDL-C and slightly LDL-C/HDL-C and VLDL-C in the subjects could lead to increase coronary heart diseases. Results were matched for the age and sex of subjects.

  7. Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes

    International Nuclear Information System (INIS)

    Junker, L.H.; Davis, R.A.

    1989-01-01

    The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of [14C]cholesterol from [2-14C]acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of [14C]cholesterol from [2-14C]acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis

  8. Physical inactivity interacts with an endothelial lipase polymorphism to modulate high density lipoprotein cholesterol in the GOLDN study

    Science.gov (United States)

    BACKGROUND: Plasma high density lipoprotein (HDL) cholesterol (HDL-C) concentration is highly heritable but is also modifiable by environmental factors including physical activity. HDL-C response to exercise varies among individuals, and this variability may be associated with genetic polymorphism...

  9. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Science.gov (United States)

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. © Georg Thieme Verlag KG Stuttgart · New York.

  10. Comparison of gemfibrozil versus simvastatin in familial combined hyperlipidemia and effects on apolipoprotein-B-containing lipoproteins, low-density lipoprotein subfraction profile, and low-density lipoprotein oxidizability

    NARCIS (Netherlands)

    Bredie, S. J.; de Bruin, T. W.; Demacker, P. N.; Kastelein, J. J.; Stalenhoef, A. F.

    1995-01-01

    We evaluated in a double-blind, placebo-controlled, randomized trial of 45 well-defined patients with familial combined hyperlipidemia, the effect of gemfibrozil (1,200 mg/day) or simvastatin (20 mg/day) on apolipoprotein-B (apo-B)-containing lipoproteins, low-density lipoprotein (LDL) subfraction

  11. Comparison of Friedewald Formula and Modified Friedewald Formula with Direct Homogeneous Assay for Low Density Lipoprotein Cholesterol Estimation

    International Nuclear Information System (INIS)

    Anwar, M.; Khan, D. A.; Khan, F. A.

    2014-01-01

    Objective: To compare the Friedewald and modified Friedewald formulae with direct homogeneous assay for serum lowdensity lipoprotein cholesterol (LDL-C) levels estimation. Study Design: Cross-sectional study. Place and Duration of Study: Armed Forces Institute of Pathology, Rawalpindi, from June to December 2011. Methodology: Healthy subjects of either gender, from Rawalpindi, aged 18-75 years were included by consecutive sampling. Patients with diabetes mellitus, chronic liver disease, chronic kidney disease, those taking lipid lowering drugs and samples with triglyceride (TG) > 4.52 mmol/l were excluded from the study. Total cholesterol, high-density lipoprotein cholesterol, TG and LDL-C were measured on Hitachi 912 chemistry analyzer (Roche). LDL-C levels were also calculated by Friedewald formula (FF) and Vujovic modified formula (VMF). Paired sample t-test and scatter plots were used for statistical analysis. Results: Although both calculated methods showed good correlation with direct assay (r > 0.93) in 300 subjects, but the difference was statistically significant. The ffLDL-C were 0.12 +- 31 mmol/l (p < 0.001) lower and vmfLDL-C were 0.11 +- 26 mmol/l (p < 0.001) higher than dLDL-C. The difference was not significant between ffLDL-C and dLDL-C at TG levels < 1.70 mmol/l (p = 0.58) and between vmfLDL-C and dLDL-C at TG levels 2.26 - 4.52 mmol/l (p = 0.38). At all other TG levels, the difference between LDL-C calculated by both formulas and dLDL-C was statistically significant (p < 0.001). As compared to direct assay, 11% and 14% subjects were classified in wrong National Cholesterol Education Programm cardiac risk categories by FF and VMF respectively. Conclusion: LDL-C should be measured by direct homogeneous assay in routine clinical laboratories, as the calculated methods did not have a uniform performance for LDL-C estimation at different TG levels. (author)

  12. Phytosterols, Phytostanols, and Lipoprotein Metabolism

    Directory of Open Access Journals (Sweden)

    Helena Gylling

    2015-09-01

    Full Text Available The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%–10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein

  13. Phytosterols, Phytostanols, and Lipoprotein Metabolism.

    Science.gov (United States)

    Gylling, Helena; Simonen, Piia

    2015-09-17

    The efficacy of phytosterols and phytostanols added to foods and food supplements to obtain significant non-pharmacologic serum and low density lipoprotein (LDL) cholesterol reduction is well documented. Irrespective of age, gender, ethnic background, body weight, background diet, or the cause of hypercholesterolemia and, even added to statin treatment, phytosterols and phytostanols at 2 g/day significantly lower LDL cholesterol concentration by 8%-10%. They do not affect the concentrations of high density lipoprotein cholesterol, lipoprotein (a) or serum proprotein convertase subtilisin/kexin type 9. In some studies, phytosterols and phytostanols have modestly reduced serum triglyceride levels especially in subjects with slightly increased baseline concentrations. Phytosterols and phytostanols lower LDL cholesterol by displacing cholesterol from mixed micelles in the small intestine so that cholesterol absorption is partially inhibited. Cholesterol absorption and synthesis have been carefully evaluated during phytosterol and phytostanol supplementation. However, only a few lipoprotein kinetic studies have been performed, and they revealed that LDL apoprotein B-100 transport rate was reduced. LDL particle size was unchanged, but small dense LDL cholesterol concentration was reduced. In subjects with metabolic syndrome and moderate hypertriglyceridemia, phytostanols reduced not only non- high density lipoprotein (HDL) cholesterol concentration but also serum triglycerides by 27%, and reduced the large and medium size very low density lipoprotein particle concentrations. In the few postprandial studies, the postprandial lipoproteins were reduced, but detailed studies with apoprotein B-48 are lacking. In conclusion, more kinetic studies are required to obtain a more complete understanding of the fasting and postprandial lipoprotein metabolism caused by phytosterols and phytostanols. It seems obvious, however, that the most atherogenic lipoprotein particles will be

  14. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations.

    Science.gov (United States)

    Jacobs, Doris M; Smolders, Lotte; Lin, Yuguang; de Roo, Niels; Trautwein, Elke A; van Duynhoven, John; Mensink, Ronald P; Plat, Jogchum; Mihaleva, Velitchka V

    2017-01-01

    Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH). We have investigated the effect of theobromine (TB) consumption on the concentrations of triglyceride (TG) and cholesterol (CH) in various lipoprotein (LP) subclasses. Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m 2 ) with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1 H NMR spectra of fasting serum. Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM) particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses. Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  15. Effect of Theobromine Consumption on Serum Lipoprotein Profiles in Apparently Healthy Humans with Low HDL-Cholesterol Concentrations

    Directory of Open Access Journals (Sweden)

    Doris M. Jacobs

    2017-08-01

    Full Text Available Scope: Theobromine is a major active compound in cocoa with allegedly beneficial effect on high-density-lipoprotein-cholesterol (HDL-CH. We have investigated the effect of theobromine (TB consumption on the concentrations of triglyceride (TG and cholesterol (CH in various lipoprotein (LP subclasses.Methods: In a randomized, double-blind, placebo-controlled, cross-over study, 44 apparently healthy women and men (age: 60 ± 6 years, BMI: 29 ± 3 kg/m2 with low baseline HDL-CH concentrations consumed a drink supplemented with 500 mg/d theobromine for 4 weeks. TG and CH concentrations in 15 LP subclasses were predicted from diffusion-edited 1H NMR spectra of fasting serum.Results: The LP phenotype of the subjects was characterized by low CH concentrations in the large HDL particles and high TG concentrations in large VLDL and chylomicron (CM particles, which clearly differed from a LP phenotype of subjects with normal HDL-CH. TB only reduced CH concentrations in the LDL particles by 3.64 and 6.79%, but had no effect on TG and CH in any of the HDL, VLDL and CM subclasses.Conclusion: TB was not effective on HDL-CH in subjects with a LP phenotype characterized by low HDL-CH and high TG in VLDL.

  16. Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol levels in individuals with untreated HIV infection.

    Science.gov (United States)

    Sandler, Netanya G; Zhang, Xinyan; Bosch, Ronald J; Funderburg, Nicholas T; Choi, Andrew I; Robinson, Janet K; Fine, Derek M; Coombs, Robert W; Jacobson, Jeffrey M; Landay, Alan L; Douek, Daniel C; Tressler, Randall; Read, Sarah W; Wilson, Cara C; Deeks, Steven G; Lederman, Michael M; Gandhi, Rajesh T

    2014-11-15

    Abnormal levels of inflammation are associated with cardiovascular disease and mortality in human immunodeficiency virus (HIV)-infected patients. Microbial translocation, which may cause inflammation, is decreased by sevelamer in patients undergoing hemodialysis. In this single-arm study, we evaluated the effects of 8 weeks of sevelamer therapy on 36 HIV-infected subjects who were not receiving antiretroviral therapy. Sevelamer did not significantly change markers of microbial translocation, inflammation, or T-cell activation. During sevelamer treatment, however, levels of soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol decreased significantly, whereas D-dimer levels increased. Thus, in this study population, sevelamer did not reduce microbial translocation but may have yielded cardiovascular benefits. NCT 01543958. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Liver lipase and high-density lipoprotein. Lipoprotein changes after incubation of human serum with rat liver lipase.

    Science.gov (United States)

    Groot, P H; Scheek, L M; Jansen, H

    1983-05-16

    Human sera were incubated with rat liver lipase after inactivation of lecithin:cholesterol acyltransferase, and the changes in serum lipoprotein composition were measured. In the presence of liver lipase serum triacylglycerol and phosphatidylcholine were hydrolyzed. The main changes in the concentrations of these lipids were found in the high-density lipoprotein fraction. Subfractionation of high-density lipoprotein by rate-zonal ultracentrifugation showed a prominent decrease in all constituents of high-density lipoprotein2, a smaller decrease in the 'light' high-density lipoprotein3 and an increase in the 'heavy' high-density lipoprotein3. These data support a concept in which liver lipase is involved in high-density lipoprotein2 phospholipid and triacylglycerol catabolism and suggest that as a result of this action high-density lipoprotein2 is converted into high-density lipoprotein3.

  18. Effects of intensive atorvastatin and rosuvastatin treatment on apolipoprotein B-48 and remnant lipoprotein cholesterol levels

    Science.gov (United States)

    Atorvastatin and rosuvastatin at maximal doses are both highly effective in lowering low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels. Rosuvastatin has been shown to be more effective than atorvastatin in lowering LDL-C, small dense LDL-C and in raising high-density lipoprote...

  19. Activation of lipoprotein lipase by lipoprotein fractions of human serum.

    Science.gov (United States)

    Bier, D M; Havel, R J

    1970-11-01

    Triglycerides in fat emulsions are hydrolyzed by lipoprotein lipase only when they are "activated" by serum lipoproteins. The contribution of different lipoprotein fractions to hydrolysis of triglycerides in soybean oil emulsion was assessed by determining the quantity of lipoprotein fraction required to give half-maximal hydrolysis. Most of the activator property of whole serum from normolipidemic, postabsorptive subjects was in high density lipoproteins. Low density lipoproteins and serum from which all lipoprotein classes were removed had little or no activity. Also, little activator was present in guinea pig serum or in very low density poor serum from an individual with lecithin:cholesterol acyltransferase deficiency, both of which are deficient in high density lipoproteins. Human very low density lipoproteins are potent activators and are much more active than predicted from their content of high density lipoprotein-protein. Per unit weight of protein, very low density lipoproteins had 13 times the activity of high density lipoproteins. These observations suggest that one or more of the major apoproteins of very low density lipoproteins, present as a minor constituent of high density lipoproteins, may be required for the activation process.

  20. Clinical benefit from pharmacological elevation of high-density lipoprotein cholesterol: meta-regression analysis.

    Science.gov (United States)

    Hourcade-Potelleret, F; Laporte, S; Lehnert, V; Delmar, P; Benghozi, Renée; Torriani, U; Koch, R; Mismetti, P

    2015-06-01

    Epidemiological evidence that the risk of coronary heart disease is inversely associated with the level of high-density lipoprotein cholesterol (HDL-C) has motivated several phase III programmes with cholesteryl ester transfer protein (CETP) inhibitors. To assess alternative methods to predict clinical response of CETP inhibitors. Meta-regression analysis on raising HDL-C drugs (statins, fibrates, niacin) in randomised controlled trials. 51 trials in secondary prevention with a total of 167,311 patients for a follow-up >1 year where HDL-C was measured at baseline and during treatment. The meta-regression analysis showed no significant association between change in HDL-C (treatment vs comparator) and log risk ratio (RR) of clinical endpoint (non-fatal myocardial infarction or cardiac death). CETP inhibitors data are consistent with this finding (RR: 1.03; P5-P95: 0.99-1.21). A prespecified sensitivity analysis by drug class suggested that the strength of relationship might differ between pharmacological groups. A significant association for both statins (p<0.02, log RR=-0.169-0.0499*HDL-C change, R(2)=0.21) and niacin (p=0.02, log RR=1.07-0.185*HDL-C change, R(2)=0.61) but not fibrates (p=0.18, log RR=-0.367+0.077*HDL-C change, R(2)=0.40) was shown. However, the association was no longer detectable after adjustment for low-density lipoprotein cholesterol for statins or exclusion of open trials for niacin. Meta-regression suggested that CETP inhibitors might not influence coronary risk. The relation between change in HDL-C level and clinical endpoint may be drug dependent, which limits the use of HDL-C as a surrogate marker of coronary events. Other markers of HDL function may be more relevant. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  1. Impact of Hypertriglyceridemia on Carotid Stenosis Progression under Normal Low-Density Lipoprotein Cholesterol Levels.

    Science.gov (United States)

    Kitagami, Masayuki; Yasuda, Ryuta; Toma, Naoki; Shiba, Masato; Nampei, Mai; Yamamoto, Yoko; Nakatsuka, Yoshinari; Sakaida, Hiroshi; Suzuki, Hidenori

    2017-08-01

    Dyslipidemia is a well-known risk factor for carotid stenosis progression, but triglycerides have attracted little attention. The aim of this study was to assess if serum triglycerides affect progression of carotid stenosis in patients with well-controlled low-density lipoprotein cholesterol (LDL-C) levels. This is a retrospective study in a single hospital consisting of 71 Japanese patients with internal carotid artery stenosis greater than or equal to 50% and normal serum LDL-C levels who underwent angiographic examination with or without the resultant carotid artery stenting or endarterectomy from 2007 to 2011, and were subsequently followed up for 4 years. Clinical factors including fasting serum triglyceride values were compared between the progression (≥10% increase in degree of carotid stenosis on ultrasonography) and the nonprogression groups. During 4 years, 15 patients (21.1%) had carotid stenosis progression on either side. Cox regression analysis demonstrated that symptomatic cases (hazard ratio [HR], 4.327; P = .019), coexisting intracranial arteriosclerotic stenosis (HR, 5.341; P = .005), and hypertriglyceridemia (HR, 6.228; P = .011) were associated with subsequent progression of carotid stenosis. Kaplan-Meier plots demonstrated that the progression-free survival rate was significantly higher in patients without hypertriglyceridemia and intracranial arteriosclerotic stenosis at baseline. Among patients with moderate to severe carotid stenosis and well-controlled LDL-C, hypertriglyceridemia was an important risk factor for progression of carotid stenosis irrespective of surgical treatments. It would be worthwhile to test if triglyceride-lowering medications suppress carotid stenosis progression. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  2. Low density lipoprotein receptors: preliminary results on 'in vivo' study

    International Nuclear Information System (INIS)

    Lupattelli, G.; Virgolini, I.; Li, S.R.; Sinzinger, H.

    1991-01-01

    Plasmatic levels of low density lipoproteins (LDL) are regulated by the receptor pathway and most LDL receptor are located in the liver. A receptor defect due to genetic mutations of the LDL receptor gene is the cause of familial hypercholesterolemia (F.H.), a disease characterized by high cholesterol levels and premature atherosclerosis. Injections of autologous radiolabelled LDL, followed by hepatic scintiscanning, can be used to obtain 'in vivo' quantification of hepatic receptor activity, both in normal and hypercholesterolemic patients. In this study we observe no hepatic increase of radioactivity in patients affected by F.H., confirming the liver receptor defect. Scintigraphy is a non-invasive technique which can be used to diagnose this disease and to monitor the efficiacy of hypolipidemic therapy. (Authors)

  3. Controlling for high-density lipoprotein cholesterol does not affect the magnitude of the relationship between alcohol and coronary heart disease.

    Science.gov (United States)

    Magnus, Per; Bakke, Eirin; Hoff, Dominic A; Høiseth, Gudrun; Graff-Iversen, Sidsel; Knudsen, Gun Peggy; Myhre, Ronny; Normann, Per Trygve; Næss, Øyvind; Tambs, Kristian; Thelle, Dag S; Mørland, Jørg

    2011-11-22

    This study tested the hypothesis that moderate alcohol intake exerts its cardioprotective effect mainly through an increase in the serum level of high-density lipoprotein cholesterol. In the Cohort of Norway (CONOR) study, 149 729 adult participants, recruited from 1994 to 2003, were followed by linkage to the Cause of Death Registry until 2006. At recruitment, questionnaire data on alcohol intake were collected, and the concentration of high-density lipoprotein cholesterol in serum was measured. Using Cox regression, we found that the adjusted hazard ratio for men for dying from coronary heart disease was 0.52 (95% confidence interval, 0.39-0.69) when consuming alcohol more than once a week compared with never or rarely. The ratio changed only slightly, to 0.55 (0.41-0.73), after the regression model included the serum level of high-density cholesterol. For women, the corresponding hazard ratios were 0.62 (0.32-1.23) and 0.68 (0.34-1.34), respectively. Alcohol intake is related to a reduced risk of death from coronary heart disease in the follow-up of a large, population-based Norwegian cohort study with extensive control for confounding factors. Our findings suggest that the serum level of high-density cholesterol is not an important intermediate variable in the possible causal pathway between moderate alcohol intake and coronary heart disease.

  4. Stimulation of cholesteryl ester synthesis in mouse peritoneal macrophages by cholesterol-rich very low density lipoproteins from the Watanabe heritable hyperlipidemic rabbit, an animal model of familial hypercholesterolemia

    International Nuclear Information System (INIS)

    Kita, T.; Yokode, M.; Watanabe, Y.; Narumiya, S.; Kawai, C.

    1986-01-01

    Cholesterol-rich very low density lipoproteins (VLDL) from the homozygous Watanabe heritable hyperlipidemic (WHHL) rabbit induced marked cholesteryl ester accumulation in mouse peritoneal macrophages. This WHHL rabbit, an animal model of human familial hypercholesterolemia, has severe hypercholesterolemia, cutaneous xanthomas, and fulminant atherosclerosis due to the deficiency of the low density lipoprotein (LDL) receptor. When incubated with mouse peritoneal macrophages, the VLDL from WHHL rabbit (WHHL-VLDL) stimulated cholesteryl [ 14 C]oleate synthesis 124-fold more than did VLDL from the normal Japanese White rabbit (control-VLDL). The enhancement in cholesteryl ester synthesis and accumulation of WHHL-VLDL was due to the presence of a high affinity binding receptor site on the macrophage cell surface that mediated the uptake and lysosomal degradation of WHHL-VLDL. Competition studies showed that the uptake and degradation of 125 I-WHHL-VLDL was inhibited by unlabeled excess WHHL-VLDL and beta-migrating VLDL (beta-VLDL), but not LDL. Furthermore, the degradation of WHHL-VLDL was not blocked by either fucoidin, polyinosinic acid, or polyguanylic acid, potent inhibitors of the acetylated (acetyl)-LDL binding site, or by acetyl-LDL. These results suggest that macrophages possess a high affinity receptor that recognizes the cholesterol-rich VLDL present in the plasma of the WHHL rabbit and that the receptor which mediates ingestion of WHHL-VLDL seems to be the same as that for beta-VLDL and leads to cholesteryl ester deposition within macrophages. Thus, the uptake of the cholesterol-rich VLDL from the WHHL rabbit by macrophages in vivo may play a significant role in the pathogenesis of atherosclerosis in the WHHL rabbit

  5. The Correlation between the Triglyceride to High Density Lipoprotein Cholesterol Ratio and Computed Tomography-Measured Visceral Fat and Cardiovascular Disease Risk Factors in Local Adult Male Subjects

    OpenAIRE

    Park, Hye-Rin; Shin, Sae-Ron; Han, A Lum; Jeong, Yong Joon

    2015-01-01

    Background We studied the association between the triglyceride to high-density lipoprotein cholesterol ratio and computed tomography-measured visceral fat as well as cardiovascular risk factors among Korean male adults. Methods We measured triglycerides, high density lipoprotein cholesterol, body mass, waist circumference, fasting plasma glucose, hemoglobin A1c, systolic blood pressure, diastolic blood pressure, visceral fat, and subcutaneous fat among 372 Korean men. The visceral fat and sub...

  6. Effects of aerobic exercise on lipids and lipoproteins.

    Science.gov (United States)

    Wang, Yating; Xu, Danyan

    2017-07-05

    Dyslipidemia is the risk of cardiovascular disease, and their relationship is clear. Lowering serum cholesterol can reduce the risk of coronary heart disease. At present, the main treatment is taking medicine, however, drug treatment has its limitations. Exercise not only has a positive effect on individuals with dyslipidemia, but can also help improve lipids profile. This review is intending to provide information on the effects of exercise training on both tranditional lipids, for example, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides and new lipids and lipoproteins such as non-high-density lipoprotein cholesterol, and postprandial lipoprotein. The mechanisms of aerobic exercise on lipids and lipoproteins are also briefly described.

  7. Effective reduction of LDL cholesterol by indigenous plant product.

    Science.gov (United States)

    Bhardwaj, P K; Dasgupta, D J; Prashar, B S; Kaushal, S S

    1994-03-01

    A herbal powder containing guar gum, methi, tundika and meshasringi was administered to 30 control and 30 type 2 (non-insulin dependent) diabetes mellitus patients for a month. Total serum cholesterol and its fractions eg, high density lipoprotein, low density lipoproteins, very low density lipoproteins and serum triglyceride were determined before and after the trial period. Total and low density lipoprotein (LDL) cholesterols were reduced significantly after the therapy. There were no significant changes in high density lipoproteins (HDL), very low density lipoproteins (VLDL) or triglyceride levels. Side-effects eg, mild flatulence and looseness of bowel were noticed in less than 40% cases.

  8. Effect of high density lipoproteins on permeability of rabbit aorta to low density lipoproteins

    International Nuclear Information System (INIS)

    Klimov, A.N.; Popov, V.A.; Nagornev, V.A.; Pleskov, V.M.

    1985-01-01

    A study was made on the effect of high density lipoproteins (HDL) on the permeability of rabbit aorta to low density lipoproteins (LDL) after intravenous administration of human HDL and human ( 125 I)LDL to normal and hypercholesterolemic rabbits. Evaluation of radioactivity in plasma and aorta has shown that the administration of a large dose of HDL decreased the aorta permeability rate for ( 125 I)LDL on an average by 19% in normal rabbits, and by 45% in rabbits with moderate hypercholesterolemia. A historadiographic study showed that HDL also decreased the vessel wall permeability to ( 125 I)LDL in normal and particularly in hypercholesterolemic animals. The suggestion was made that HDL at very high molar concentration can hamper LDL transportation through the intact endothelial layer into the intima due to the ability of HDL to compete with LDL in sites of low affinity on the surface of endothelial cells. (author)

  9. Self-Reported Snoring Is Associated with Dyslipidemia, High Total Cholesterol, and High Low-Density Lipoprotein Cholesterol in Obesity: A Cross-Sectional Study from a Rural Area of China.

    Science.gov (United States)

    Zhang, Naijin; Chen, Yintao; Chen, Shuang; Jia, Pengyu; Guo, Xiaofan; Sun, Guozhe; Sun, Yingxian

    2017-01-17

    Studies to explore the relationship between self-reported snoring and dyslipidemia, especially high total cholesterol (TC) and high low-density lipoprotein cholesterol (LDL-C), in the general population are still lacking. Our study was designed to examine whether self-reported snoring is significantly associated with dyslipidemia and ascertain the effects of different snoring intensities on dyslipidemia. There were 10,139 participants in our study. After adjustment for all confounding factors, self-reported snoring (OR = 1.207; p = 0.003), moderate (OR = 1.229; p = 0.015), strong (OR = 1.222; p = 0.033), and very strong (OR = 1.467; p = 0.012) snoring intensity, but not low (OR = 1.110; p = 0.224) snoring intensity, were significantly associated with dyslipidemia among adults with BMI (body mass index) ≥ 25 kg/m². In addition, self-reported snoring was significantly associated with high TC (OR = 1.167; p = 0.048) and high LDL-C (OR = 1.228; p = 0.044), rather than low HDL-C (OR = 1.171; p = 0.057) and high triglyceride (TG) (OR = 1.110; p = 0.141). In conclusion, adults with BMI ≥ 25 kg/m² and who experience snoring, especially moderate, strong, and very strong intensity levels of snoring, should be on the alert regarding the possibility of dyslipidemia, especially high LDL-C and high TC.

  10. Comparing the Impact of Prescription Omega-3 Fatty Acid Products on Low-Density Lipoprotein Cholesterol.

    Science.gov (United States)

    Sharp, Randall P; Gales, Barry J; Sirajuddin, Riaz

    2018-04-01

    Elevated levels of triglycerides are associated with pancreatitis and an increased risk of coronary heart disease. Numerous pharmacologic therapies are available to treat hypertriglyceridemia, including prescription omega-3 fatty acids, which reduce triglyceride levels by 20-50%. Available data indicate the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may be beneficial for secondary prevention of coronary heart disease. Products containing DHA may increase low-density lipoprotein cholesterol (LDL-C) and, subsequently, coronary heart disease risk. We reviewed prescription omega-3 fatty acid products, of which two-omega-3 acid ethyl esters (OM3EE) and omega-3 carboxylic acid (OM3CA)-contain both DHA and EPA, whereas the other-icosapent ethyl (IPE)-contains EPA only. We identified three retrospective chart reviews and three case reports comparing IPE with OM3EE, whereas two studies compared IPE with placebo. We also reviewed the major studies of OM3EE versus placebo used to gain US FDA approval. LDL-C levels decreased or did not increase significantly in all available studies and case reports in patients receiving the IPE product, with the best data supporting a dose of 4 g per day. The majority of studies only included patients taking IPE concomitantly with statins, but limited data from one study using IPE monotherapy showed a small reduction in LDL-C. Many questions remain regarding IPE, including whether the product reduces cardiovascular events and mortality.

  11. A pooled analysis of the association of isolated low levels of high-density lipoprotein cholesterol with cardiovascular mortality in Japan.

    Science.gov (United States)

    Hirata, Takumi; Sugiyama, Daisuke; Nagasawa, Shin-Ya; Murakami, Yoshitaka; Saitoh, Shigeyuki; Okayama, Akira; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Miyamoto, Yoshihiro; Yamada, Michiko; Ishikawa, Shizukiyo; Miura, Katsuyuki; Ueshima, Hirotsugu; Okamura, Tomonori

    2017-07-01

    Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

  12. PFOS induced lipid metabolism disturbances in BALB/c mice through inhibition of low density lipoproteins excretion

    Science.gov (United States)

    Wang, Ling; Wang, Yu; Liang, Yong; Li, Jia; Liu, Yuchen; Zhang, Jie; Zhang, Aiqian; Fu, Jianjie; Jiang, Guibin

    2014-04-01

    Male BALB/c mice fed with either a regular or high fat diet were exposed to 0, 5 or 20 mg/kg perfluorooctane sulfonate (PFOS) for 14 days. Increased body weight, serum glucose, cholesterol and lipoprotein levels were observed in mice given a high fat diet. However, all PFOS-treated mice got reduced levels of serum lipid and lipoprotein. Decreasing liver glycogen content was also observed, accompanied by reduced serum glucose levels. Histological and ultrastructural examination detected more lipid droplets accumulated in hepatocytes after PFOS exposure. Moreover, transcripitonal activity of lipid metabolism related genes suggests that PFOS toxicity is probably unrelevant to PPARα's transcription. The present study demonstrates a lipid disturbance caused by PFOS and thus point to its role in inhibiting the secretion and normal function of low density lipoproteins.

  13. Tuberculosis treatment raises total cholesterol level and restores ...

    African Journals Online (AJOL)

    aghomotsegin

    2013-10-09

    Oct 9, 2013 ... and restores high density lipoprotein cholesterol (HDL- ... cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were determined .... However, we found a strong negative correlation (r = - 0.96,.

  14. Distribution and correlates of non-high-density lipoprotein cholesterol and triglycerides in Lebanese school children.

    Science.gov (United States)

    Gannagé-Yared, Marie-Hélène; Farah, Vanessa; Chahine, Elise; Balech, Nicole; Ibrahim, Toni; Asmar, Nadia; Barakett-Hamadé, Vanda; Jambart, Selim

    2016-01-01

    The prevalence of dyslipidelmia in pediatric Middle-Eastern populations is unknown. Our study aims to investigate the distribution and correlates of non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides among Lebanese school children. A total of 969 subjects aged 8-18 years were included in the study (505 boys and 464 girls). Recruitment was done from 10 schools located in the Great Beirut and Mount-Lebanon areas. Non-fasting total cholesterol, triglycerides, and HDL-cholesterol (HDL-C) were measured. Non-HDL-C was calculated. Schools were categorized into 3 socioeconomic statuses (SESs; low, middle, and high). In the overall population, the prevalence of high non-HDL-C (>3.8 mmol/L), very high non-HDL-C (>4.9 mmol/L), and high triglycerides (>1.5 mmol/l) are respectively 9.2%, 1.24%, and 26.6%. There is no significant gender difference for non-HDL-C or triglycerides. Non-HDL-C and triglycerides are inversely correlated with age in girls (P triglycerides are higher in children from lower SES schools. After adjustment for age and body mass index (BMI), testosterone is inversely associated with triglycerides in boys (P triglycerides are independently associated with BMI and schools' SES in both girls and boys. This study confirms, in our population, the association between obesity and both high non-HDL-C and triglycerides, and between high triglycerides and low SES. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  15. Effects of human low and high density lipoproteins on the binding of rat intermediate density lipoproteins to rat liver membranes

    International Nuclear Information System (INIS)

    Brissette, L.; Nol, S.P.

    1986-01-01

    Upon incubation with rat liver membranes, radioiodinated rat intermediate density lipoproteins (IDL) interacted with at least two binding sites having a low and a high affinity as demonstrated by the curvilinear Scatchard plots obtained from the specific binding data. The purpose of our work was to identify the nature of these binding sites. Human low density lipoproteins (LDL), contain apolipoprotein B only, and human high density lipoproteins (HDL3), containing neither apolipoprotein B nor E, were both capable of decreasing the specific binding of rat 125 I-IDL. The Scatchard analysis clearly revealed that only the low affinity component was affected by the addition of these human lipoproteins. In fact, the low affinity binding component gradually decreased as the amount of human LDL or HDL3 increased in the binding assay. At a 200-fold excess of human LDL or HDL3, the low affinity binding was totally masked, and the Scatchard plot of the specific 125 I-IDL binding became linear. Only the high affinity binding component was left, enabling a precise measurement of its binding parameters. In a series of competitive displacement experiments in which the binding assay contained a 200-fold excess of human LDL or HDL3, only unlabeled rat IDL effectively displaced the binding of rat 125 I-IDL. We conclude that the low affinity binding of rat IDL to rat liver membranes is due to weak interactions with unspecified lipoprotein binding sites. The camouflage of these sites by human lipoproteins makes possible the study of IDL binding to the high affinity component which likely represents the combined effect of IDL binding to both the remnant and the LDL receptors

  16. Dietary fish oil stimulates hepatic low density lipoprotein transport in the rat.

    Science.gov (United States)

    Ventura, M A; Woollett, L A; Spady, D K

    1989-01-01

    These studies were undertaken to examine the effect of fish oil, safflower oil, and hydrogenated coconut oil on the major processes that determine the concentration of low density lipoprotein (LDL) in plasma, i.e., the rate of LDL production and the rates of receptor-dependent and receptor-independent LDL uptake in the various organs of the body. When fed at the 20% level, fish oil reduced plasma LDL-cholesterol levels by 38% primarily by increasing LDL receptor activity in the liver. Dietary safflower oil also increased hepatic LDL receptor activity; however, since the rate of LDL production also increased, plasma LDL-cholesterol levels remained essentially unchanged. Hydrogenated coconut oil had no effect on LDL receptor activity but increased the rate of LDL-cholesterol production causing plasma LDL-cholesterol levels to increase 46%. Dietary fish oil had no effect on the receptor-dependent transport of asialofetuin by the liver, suggesting that the effect of fish oil on hepatic LDL receptor activity was specific and not due to a generalized alteration in the physical properties of hepatic membranes. Finally, dietary fish oil increased hepatic cholesteryl ester levels and suppressed hepatic cholesterol synthesis rates, suggesting that the up-regulation of hepatic LDL receptor activity in these animals was not simply a response to diminished cholesterol availability in the liver. PMID:2760200

  17. What's Cholesterol?

    Science.gov (United States)

    ... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  18. Experimental hypothyroidism modulates the expression of the low density lipoprotein receptor by the liver

    International Nuclear Information System (INIS)

    Scarabottolo, Lia; Trezzi, Ermanno; Roma, Paola; Catapano, A.L.

    1986-01-01

    The effect of exprimental hypothyroidism of the catabolism of plasma lipoproteins and on the expression of low density lipoprotein receptors by the liver was investigated in rats made hypothyroid by surgery. The animals developed mild hypercholesterolemia, mainly due to an increase of plasma low density lipoprotein, while other lipoprotein classes were only marginally affected. Kinetic studies using ( 125 I)LDL indicated that a decreased fractional catabolic rate of the lipoprotein was responsible for this finding in agreement with the in vitro observation of a reduced binding of lipoproteins to liver membranes from hyperthyroid rats and with the demonstrations, by ligand blotting analysis, of a decreasd expression of lipoprotein receptors in liver membranes. These data suggest that hypothyroidism affects lipoprotein distribution also by decreasing the catabolism of low density lipoproteins by the liver (author)

  19. Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

    Science.gov (United States)

    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

  20. Experimental atheromatous plaque imaging with 99mTc labelled low density lipoproteins in rabbit

    International Nuclear Information System (INIS)

    Wang Quanshi; Chen Yu; Wu Chunshan; Zhang Yijin; Liu Dexuan

    1996-01-01

    Atheromatous plaque imaging with 99m Tc labeled low density lipoproteins ( 99m Tc-LDL) were evaluated in rabbits for its clinical prospect. The 99m Tc-LDL atheromatous plaque imaging were performed in 9 rabbit models of atherosclerosis and 4 controls. The imagings were compared with autoradiographic and pathological results. The rabbit models of atherosclerosis by high cholesterol and high fat diet were successful in 100%. The atheromatous plaques well visualized in 8 of 9 rabbit models 24 hours after injection. The site and density of radioactive accumulation was closely correlated in autoradiography also. There was no radioactive spot in 4 controls. 99m Tc-LDL imaging may have a significant value for the diagnosis of atherosclerosis

  1. What Is Cholesterol?

    Science.gov (United States)

    ... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

  2. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2008-01-01

    Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

  3. Plasma 27-hydroxycholesterol/cholesterol ratio is increased in low high density lipoprotein-cholesterol healthy subjects.

    Science.gov (United States)

    Nunes, Valéria S; Leança, Camila C; Panzoldo, Natália B; Parra, Eliane; Zago, Vanessa; Cazita, Patrícia M; Nakandakare, Edna R; de Faria, Eliana C; Quintão, Eder C R

    2013-10-01

    Sterol 27-hydroxylase converts cholesterol to 27-hydroxycholesterol (27-OHC) which is widely distributed among tissues and is expressed at high levels in the vascular endothelium and macrophages. There is a continuous flow of this oxysterol from the tissues into the liver, where it is converted to bile acids. Measure plasma concentrations of 27-OHC in subjects that differ according to their plasma HDL-C concentration. Healthy men presenting low HDL-C (1.55 mmol/L), n=18, BMIm² were recruited after excluding secondary causes that might interfere with their plasma lipid concentrations such as smoking, heavy drinking and diabetes. Blood samples were drawn after a 12h fasting period for the measurement of 27-OHC by the combined GC/MS analysis utilizing deuterium-label internal standards. The plasma ratio 27-OHC/total cholesterol (median and range nmoL/mmoL) was 50.41 (27.47-116.00) in the High HDL-C subjects and 63.34 (36.46-91.18) in the Low HDL-C subjects (p=0.0258). Our data indicate that the production of 27-OHC by extrahepatic tissues and its transport to the liver may represent an alternative pathway for a deficient reverse cholesterol transport system when plasma HDL-C is low. © 2013.

  4. Uptake of low density lipoproteins by the hamster lung. Interactions with capillary endothelium

    International Nuclear Information System (INIS)

    Nistor, A.; Simionescu, M.

    1986-01-01

    The mechanism by which the circulating low density lipoproteins (LDL) contribute to the lung surfactant cholesterol was investigated by perfusing the hamster lung in situ with LDL either radiolabeled or coupled to gold, or both. Part of [ 125 I]-LDL and [ 3 H]-cholesterol LDL were taken up by a specific process which was time- and concentration-dependent and reached saturation within 20 to 30 min of perfusion. Competition experiments and removal of receptor-bound LDL by heparin suggested that about 50% of LDL uptake is receptor-independent. Experiments using double labeled LDL showed a preferential uptake of 3 H-cholesterol versus 125 I by the lung both in situ and in vivo. LDL-gold particles (LDL-Au), recirculated through the isolated lung, bound to the endothelial luminal plasma membrane and to features potentially involved in receptor-mediated endocytosis (coated pits, coated vesicles, lysosomelike structures) and in transcytosis (plasmalemmal vesicles). The results suggest that LDL uptake by the lung takes place by both receptor-mediated and receptor-independent mechanisms. Cholesterol may be in part transferred to the lung without the apoprotein moiety; the alveolar capillary endothelium appears to be the first monitor of this complex process

  5. Low density lipoproteins mediated nanoplatforms for cancer targeting

    International Nuclear Information System (INIS)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant; Jain, Narendra K.

    2013-01-01

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body’s defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature’s method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL–drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier

  6. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant, E-mail: prashant_pharmacy04@rediffmail.com; Jain, Narendra K., E-mail: jnarendr@yahoo.co.in [Dr. H. S. Gour University, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences (India)

    2013-09-15

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature's method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL-drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

  7. Low density lipoproteins mediated nanoplatforms for cancer targeting

    Science.gov (United States)

    Jain, Anupriya; Jain, Keerti; Kesharwani, Prashant; Jain, Narendra K.

    2013-09-01

    Chemotherapy is a foremost remedial approach for the treatment of localized and metastasized tumors. In order to explore new treatment modalities for cancer, it is important to identify qualitative or quantitative differences in metabolic processes between normal and malignant cells. One such difference may be that of increased receptor-mediated cellular uptake of low density lipoproteins (LDLs) by cancer cells. Lipoproteins in general and specifically LDL are ideal candidates for loading and delivering cancer therapeutic and diagnostic agents due to their biocompatibility. By mimicking the endogenous shape and structure of lipoproteins, the reconstituted lipoproteins can remain in circulation for an extended period of time, while largely evading the reticuloendothelial cells in the body's defenses. In this account, we review the field of low density inspired nanoparticles in relation to the delivery of cancer imaging and therapeutic agents. LDL has instinctive cancer targeting potential and has been used to incorporate various lipophillic molecules to transport them to tumors. Nature's method of rerouting LDL provides a strategy to extend the cancer targeting potential of lipoproteins far off its constricted purview. In this review, we have discussed the various aspects of LDL including its role in cancer imaging and chemotherapy in retrospect and prospect and current efforts aimed to further improve the delivery efficacy of LDL-drug complexes with reduced chances of drug resistance leading to optimal drug delivery. This review provides a strong support for the concept of using LDL as a drug carrier.

  8. Importance of measuring Non-HDL cholesterol in type 2 diabetes patients

    International Nuclear Information System (INIS)

    Ram, N.; Hashmi, F.; Jabbar, A

    2014-01-01

    Objective: To study the correlation between Non-high-density lipoprotein and low-density lipoprotein cholesterol in patients with Type 2 diabetes mellitus and the proportion of patients achieving Adult Treatment Panel III recommended goals. Methods: The cross sectional study was conducted at the Diabetic Clinic, Aga Khan University Hospital, Karachi. Data of Type 2 diabetes mellitus patients who attended the clinic between 2007 and 2011 was reviewed. All Type 2 diabetic patients of either gender with fasting lipid profile irrespective of taking lipid lowering therapy were included. Type-1 DM, gestational diabetes, type 2 diabetes patients with pregnancy and those with incomplete data were excluded. Correlation between the low-density lipoprotein and Non- high-density lipoprotein was assessed by applying Cramer V and phi. Proportion of patients achieving Adult Treatment Panel III recommended goals was checked. Multivariable regression was done to identify common factors associated with elevated Non- high-density lipoprotein cholesterol. Results: A total of 1352 patients fulfilling the eligibility criteria were included in the study. Mean age of the patients was 54.5+-11.3 years; 797 (59%) were males; 1122 (83%) had Body Mass Index above 25; and 1016 (75%) had HbA1c >7%. Mean Non-high-density lipoprotein cholesterol was 129+-42mg/dl. Mean low-density lipoprotein cholesterol was 100+-37mg/dl. Both low-density lipoprotein 130mg/dl (p 100mg/dl was independently associated with having Non-high-density lipoprotein cholesterol >130mg/dl (Adjusted Odds Ratio 38.6; 95% Confidance Interval 28.1-53.1). Similarly, age 130 mg/dl (Adjusted Odds Ratio 1.6; 95% Confidance Interval = 1.01 - 2.3). Whereas having obesity Body Mass Index >25 was 3.6 times more associated to have Non-high-density lipoprotein >130mg/dl (Adjusted Odds Ratio 3.6; 95% Confidance Interval = 1.6-7.7). In patients with coronary artery disease, combined goal achievement of low-density lipoprotein 100mg/dl (p <0

  9. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  10. Cholesterol Efflux Capacity, High-Density Lipoprotein Particle Number, and Incident Cardiovascular Events: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin).

    Science.gov (United States)

    Khera, Amit V; Demler, Olga V; Adelman, Steven J; Collins, Heidi L; Glynn, Robert J; Ridker, Paul M; Rader, Daniel J; Mora, Samia

    2017-06-20

    Recent failures of drugs that raised high-density lipoprotein (HDL) cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low low-density lipoprotein cholesterol. HDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal low-density lipoprotein cholesterol but increased C-reactive protein levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD. Cholesterol efflux capacity was moderately correlated with HDL cholesterol, apolipoprotein A-I, and HDL particle number (Spearman r = 0.39, 0.48, and 0.39 respectively; P capacity (OR/SD, 0.89; 95% CI, 0.72-1.10; P =0.28), HDL cholesterol (OR/SD, 0.82; 95% CI, 0.66-1.02; P =0.08), or apolipoprotein A-I (OR/SD, 0.83; 95% CI, 0.67-1.03; P =0.08). Twelve months of rosuvastatin (20 mg/day) did not change cholesterol efflux capacity (average percentage change -1.5%, 95% CI, -13.3 to +10.2; P =0.80), but increased HDL cholesterol (+7.7%), apolipoprotein A-I (+4.3%), and HDL particle number (+5.2%). On-statin cholesterol efflux capacity was inversely associated with incident CVD (OR/SD, 0.62; 95% CI, 0

  11. Status of non-HDL-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome.

    Science.gov (United States)

    Khan, Sikandar Hayat; Asif, Naveed; Ijaz, Aamir; Manzoor, Syed Mohsin; Niazi, Najumusaquib Khan; Fazal, Nadeem

    2018-04-01

    To to compare non-high-density lipoprotein and low-density lipoprotein cholesterol among subjects with or without metabolic syndrome, glycation status and nephropathic changes. The comparative cross-sectional study was carried out from Dec 21, 2015, to Nov 15, 2016, at the department of pathology and medicine PNS HAFEEZ and department of chemical pathology and clinical endocrinology (AFIP), and comprised patients of either gender visiting the out-patient department for routine screening. They were evaluated for anthropometric indices, blood pressure and sampled for lipid profile, fasting plasma glucose, glycated haemoglobin, insulin, and urine albumin-to-creatinine ratio. Subjects were segregated based upon presence (Group1) or absence (Group2) of metabolic syndrome based upon criteria of National Cholesterol Education Programme and the International Diabetes Federation. Differences in high and low density lipoprotein cholesterols were calculated between the groups. Of the 229 subjects, 120(52.4%) were women and 109(47.6%) were men. Overall, there were 107(46.7%) subjects in Group 1, and 122(53.3%) in Group 2. Non-high-density lipoprotein cholesterol was significantly different between subjects with and without metabolic syndrome as per both the study criteria (p<0.05 each). . Non-high-density lipoprotein cholesterol levels were higher in subjects with metabolic syndrome.

  12. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

    Directory of Open Access Journals (Sweden)

    Miloslava Hodúlová

    Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

  13. Association between non-high-density lipoprotein cholesterol and nonalcoholic fatty liver disease in postmenopausal Uyghur women in Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Mailamuguli

    2016-06-01

    Full Text Available ObjectiveTo investigate the association between non-high-density lipoprotein cholesterol (non-HDL-C and nonalcoholic fatty liver disease (NAFLD in postmenopausal Uyghur women in Xinjiang, China. MethodsA total of 1271 postmenopausal Uyghur women who underwent physical examination in the physical examination centers of hospitals in Urumqi and Kashi, Xinjiang, were enrolled as study subjects, and according to the presence or absence of NAFLD, they were divided into NAFLD group (682 women and control group (589 women. Demographic data were recorded in detail, and the hepatic enzyme parameters, parameters for glucose and lipid metabolism, and parameters including uric acid and non-HDL-C were measured. The t-test was used for comparison of continuous data between groups, the chi-square test was used for comparison of categorical data between groups, and non-conditional logistic regression analysis was used to determine the risk factors for NAFLD in postmenopausal women. ResultsCompared with the control group, the NAFLD group had significantly higher uric acid, fasting blood glucose, triglyceride (TG, glycosylated hemoglobin, alanine aminotransferase (ALT, aspartate aminotransferase (AST, waist circumference, hip circumference, body mass index, waist-hip ratio, systolic pressure, diastolic pressure, and non-HDL-C level (all P<0.05, and a significantly lower HDL-C level (P<0.05. Compared with the group with a non-HDL-C level of ≥3.58 mmol/L, the group with a non-HDL-C level of <3.58 mmol/L had significantly lower levels of blood glucose, total cholesterol, TG, AST, ALT, and low-density lipoprotein cholesterol. The multivariate logistic regression analysis showed that non-HDL-C, serum uric acid, and BMI were risk factors for NAFLD in postmenopausal women. ConclusionNon-HDL-C, along with central obesity, hypertriglyceridemia, and hyperuricemia, is a major risk factor for NAFLD in postmenopausal women.

  14. Essential oil of Pinus koraiensis leaves exerts antihyperlipidemic effects via up-regulation of low-density lipoprotein receptor and inhibition of acyl-coenzyme A: cholesterol acyltransferase.

    Science.gov (United States)

    Kim, Ji-Hyun; Lee, Hyo-Jung; Jeong, Soo-Jin; Lee, Min-Ho; Kim, Sung-Hoon

    2012-09-01

    Hyperlipidemia is an important factor to induce metabolic syndrome such as obesity, diabetes and cardiovascular diseases. Recently, some antihyperlipidemic agents from herbal medicines have been in the spotlight in the medical science field. Thus, the present study evaluated the antihyperlipidemic activities of the essential oil from the leaves of Pinus koraiensis SIEB (EOPK) that has been used as a folk remedy for heart disease. The reverse transcription polymerase chain reaction (RT-PCR) revealed that EOPK up-regulated low density lipoprotein receptor (LDLR) at the mRNA level as well as negatively suppressed the expression of sterol regulatory element-binding protein (SREBP)-1c, SREBP-2, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS) and glycerol-3-phosphate acyltransferase (GPAT) involved in lipid metabolism in HepG2 cells. Also, western blotting showed that EOPK activated LDLR and attenuated the expression of FAS at the protein level in the cells. Consistently, EOPK significantly inhibited the level of human acylcoenzyme A: cholesterol acyltransferase (hACAT)1 and 2 and reduced the low-density lipoprotein (LDL) oxidation activity. Furthermore, chromatography-mass spectrometry (GC-MS) analysis showed that EOPK, an essential oil mixture, contained camphene (21.11%), d-limonene (21.01%), α-pinene (16.74%) and borneol (11.52%). Overall, the findings suggest that EOPK can be a potent pharmaceutical agent for the prevention and treatment of hyperlipidemia. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Investigation of the mechanism for penetration of low density lipoprotein into the arterial wall

    Science.gov (United States)

    Glukhova, O. E.; Zyktin, A. A.; Slepchenkov, M. M.

    2018-02-01

    Currently, the pathology of the cardiovascular system is an extremely urgent problem of fundamental and clinical medicine. These diseases are caused, mainly, by atherosclerotic changes in the wall of blood vessels. The predominant role in the development of atherosclerosis is attributed to the penetration of various kinds of lipoproteins into the arterial intima. In this paper, we in silico investigated the dynamics of the penetration of low density lipoprotein (LDL) through the intercellular gap using molecular modeling methods. The simulation was carried out in the GROMACS software package using a coarse-grained MARTINI model. During investigation we carried out the LDL self-assembly for the first time. The coarse-grained model of LDL was collected from the following molecules: POPC (phosphatidylcholine) - 630 molecules, LPC (lysophosphatidylcholine) - 80 molecules CHOL (cholesterol) - 600 molecules CHYO (cholesteryl oleate) - 1600 molecules TOG (glycerol trioleate) 180 Molecules. The coarse-grained model of the intercellular endothelial gap was based on a model of lipid bilayer consisting of DPPC phospholipids and cholesterol in a percentage ratio of 70% and 30%, respectively. Based on the obtained results, we can predict the mechanism of LDL diffusion. Lipoproteins can be deformed so as to pass through narrow gaps. Our investigations open the way for the research of the behavior dynamics of LDL moving with the blood flow rate when interacting with the intercellular gaps of the endothelial layer of the vessel inner wall.

  16. LDL: The "Bad" Cholesterol

    Science.gov (United States)

    ... There are two main types of cholesterol: LDL (bad) cholesterol and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to ...

  17. Membrane receptors for very low density lipoprotein (VLDL) inhibitor of lymphocyte proliferation

    International Nuclear Information System (INIS)

    Yi, P.I.; Beck, G.; Zucker, S.

    1981-01-01

    Physiologic concentrations of human plasma very low density lipoproteins inhibit the DNA synthesis of lymphocytes stimulated by allogeneic cells or lectins. In this report reachers have compared the effects of isolated lipoproteins [very low density lipoproteins (VLDL), low density lipoproteins (LDL), and high density lipoproteins (HDL)] and lipoprotein-depleted plasma (LDP) on DNA synthesis by phytohemagglutinin-stimulated human lymphocytes. The relative potency for the inhibition of lymphocyte proliferation was VLDL greater than LDL greater than HDL greater than LDP. Fifty percent inhibition of DNA synthesis was observed at a VLDL protein concentration of 1.5--2.0 microgram/ml. Researchers have further demonstrated the presence of specific receptors for VLDL on human lymphocytes. Native VLDL was more effective than LDL in competing for 125I-VLDL binding sites. Subsequent to binding to lymphocytes, 125I-VLDL was internalized and degraded to acid-soluble products. Based on a Scatchard analysis of VLDL binding at 4 degrees C, the number of VLDL receptors per lymphocyte was estimated at 28,000 +/- 1300. Based on an estimated mean binding affinity for the VLDL receptor complex at half saturation of approximately 8.8 X 10(7) liter/mole, it is estimated that 91% of lymphocyte VLDL receptors are occupied at physiologic VLDL concentrations in blood. Although the immune regulatory role of plasma lipoproteins is uncertain, researchers suggest tha VLDL and LDL-In may maintain circulating blood lymphocytes in a nonproliferative state via their respective cell receptor mechanisms

  18. Antioxidant activity of high-density lipoprotein (HDL) using different ...

    African Journals Online (AJOL)

    HDL is a potent antioxidant in terms of inhibition of lipid peroxidation, ROS production and LDL oxidation. These may to some extent add to the antiatherogenic beyond reverse-cholesterol transport properties of HDL. Keywords: high-density lipoprotein; reverse cholesterol transport; apolipoprotein A1; antioxidant; in vitro.

  19. Low serum levels of High-Density Lipoprotein cholesterol (HDL-c) as an indicator for the development of severe postpartum depressive symptoms

    Science.gov (United States)

    Ramachandran Pillai, Raji; Wilson, Anand Babu; Premkumar, Nancy R.; Kattimani, Shivanand; Sagili, Haritha

    2018-01-01

    Postpartum depression (PPD) is a psychiatric complication of childbirth affecting 10–20% of new mothers and has negative impact on both mother and infant. Serum lipid levels have been related to depressive disorders, but very limited literatures are available regarding the lipid levels in women with postpartum depression. The present study is aimed to examine the association of serum lipids with the development of postpartum depressive symptoms. This is a cross sectional study conducted at a tertiary care hospital in South India. Women who came for postpartum check-up at 6th week post-delivery were screened for PPD (September 2014-October 2015). Women with depressive symptoms were assessed using EPDS (Edinburgh Postnatal Depression Scale). The study involved 186 cases and 250 controls matched for age and BMI. Serum levels of lipid parameters were estimated through spectrophotometry and the atherogenic indices were calculated in all the subjects. Low serum levels of Total Cholesterol (TC) and High Density Lipoprotein cholesterol (HDL-c) were significantly low in PPD women with severe depressive symptoms. The study recorded a significant negative correlation between HDL-c and the EPDS score in PPD women (r = -0.140, p = 0.05). Interestingly, the study also observed a significant negative correlation between Body Mass Index (BMI) and EPDS scores in case group (r = -0.146, p = 0.047), whereas a positive correlation between the same in controls (r = 0.187, p = 0.004). Our study demonstrated that low levels of serum HDL-c is correlated with the development of severe depressive symptoms in postpartum women. Study highlights the role of lipids in the development of postpartum depressive symptoms. PMID:29444162

  20. Low serum levels of High-Density Lipoprotein cholesterol (HDL-c as an indicator for the development of severe postpartum depressive symptoms.

    Directory of Open Access Journals (Sweden)

    Raji Ramachandran Pillai

    Full Text Available Postpartum depression (PPD is a psychiatric complication of childbirth affecting 10-20% of new mothers and has negative impact on both mother and infant. Serum lipid levels have been related to depressive disorders, but very limited literatures are available regarding the lipid levels in women with postpartum depression. The present study is aimed to examine the association of serum lipids with the development of postpartum depressive symptoms. This is a cross sectional study conducted at a tertiary care hospital in South India. Women who came for postpartum check-up at 6th week post-delivery were screened for PPD (September 2014-October 2015. Women with depressive symptoms were assessed using EPDS (Edinburgh Postnatal Depression Scale. The study involved 186 cases and 250 controls matched for age and BMI. Serum levels of lipid parameters were estimated through spectrophotometry and the atherogenic indices were calculated in all the subjects. Low serum levels of Total Cholesterol (TC and High Density Lipoprotein cholesterol (HDL-c were significantly low in PPD women with severe depressive symptoms. The study recorded a significant negative correlation between HDL-c and the EPDS score in PPD women (r = -0.140, p = 0.05. Interestingly, the study also observed a significant negative correlation between Body Mass Index (BMI and EPDS scores in case group (r = -0.146, p = 0.047, whereas a positive correlation between the same in controls (r = 0.187, p = 0.004. Our study demonstrated that low levels of serum HDL-c is correlated with the development of severe depressive symptoms in postpartum women. Study highlights the role of lipids in the development of postpartum depressive symptoms.

  1. Effects of MAT9001 containing eicosapentaenoic acid and docosapentaenoic acid, compared to eicosapentaenoic acid ethyl esters, on triglycerides, lipoprotein cholesterol, and related variables.

    Science.gov (United States)

    Maki, Kevin C; Bobotas, George; Dicklin, Mary R; Huebner, Margie; Keane, William F

    Long-chain omega-3 fatty acid concentrate pharmaceuticals are used in the United States for treatment of severe hypertriglyceridemia (≥500 mg/dL) and are under investigation as adjuncts to statins for lowering cardiovascular risk in patients with high triglycerides (TGs; 200-499 mg/dL). To evaluate MAT9001, an investigational prescription-only omega-3 fatty acid agent containing predominantly eicosapentaenoic acid (EPA) and docosapentaenoic acid, in 42 men and women with fasting TG 200 to 400 mg/dL. In this open-label, crossover trial, subjects received MAT9001 and EPA ethyl esters (EPA-EE) in random order. They were housed in a clinical research unit for 2 14-day treatment periods, separated by a ≥35-day washout. Lipoprotein lipids, apolipoproteins (Apos) and proprotein convertase subtilisin kexin type 9 levels were measured before and at the end of each treatment period. MAT9001, compared with EPA-EE, resulted in significantly (P < .05) larger reductions from pretreatment levels for TG (-33.2% vs -10.5%), total cholesterol (-9.0% vs -6.2%), non-high-density lipoprotein cholesterol (-8.8% vs -4.6%), very low-density lipoprotein cholesterol (-32.5% vs -8.1%), Apo C3 (-25.5% vs -5.0%), and proprotein convertase subtilisin kexin type 9 (-12.3% vs +8.8%). MAT9001 also produced a significantly (P = .003) larger reduction in Apo A1 (-15.3% vs -10.2%), but responses for high-density lipoprotein cholesterol (-11.3% vs -11.1%), low-density lipoprotein cholesterol (-2.4% vs -4.3%), and Apo B (-3.8% vs -0.7%), respectively, were not significantly different relative to EPA-EE. MAT9001 produced significantly larger reductions than EPA-EE in several lipoprotein-related variables that would be expected to favorably alter cardiovascular disease risk in men and women with hypertriglyceridemia. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  2. Low density lipoprotein uptake by an endothelial-smooth muscle cell bilayer

    International Nuclear Information System (INIS)

    Alexander, J.J.; Miguel, R.; Graham, D.

    1991-01-01

    To study the interaction of endothelial and smooth muscle cells, and the means by which such interaction may affect lipid permeability of the arterial wall, cell bilayers were established by use of a transwell culture system. After confluent growth of both cell types had been achieved, iodine 125 bound to low-density lipoprotein (10 ng protein/ml) was added to the media of the upper well. After a 3-hour incubation period, the iodine 125-bound low-density lipoprotein content of the upper and lower media demonstrated an impedance to lipoprotein movement across the endothelial cell monolayer as compared to the bare porous polycarbonate filter of the transwell (p less than 10(-6)). The presence of smooth muscle cells in the bottom well significantly enhanced the permeability of the endothelial cell layer (p less than 10(-60)). This effect remained unchanged over a 9-day time course. Membrane binding and cellular uptake of low-density lipoprotein by endothelial cells was not altered by smooth muscle cells, indicating that this change in permeability could not be easily attributed to changes in receptor-mediated transport or transcytosis. Membrane binding (p less than 0.02) and cellular uptake (p less than 10(-6)) of low-density lipoprotein by smooth muscle cells in the bilayer, when adjusted for counts available in the smooth muscle cell media, were both reduced in the early incubation period as compared to isolated smooth muscle cells. The disproportionate reduction in uptake as compared to binding would suggest that this was not entirely a receptor-dependent process

  3. Use of the TLX ultracentrifuge for the isolation of different density lipoproteins and effects of freeze/thawing of human plasma before ultracentrifugation.

    Science.gov (United States)

    Charlton-Menys, Valentine; Chobotova, Jelena; Durrington, Paul N

    2008-01-01

    Isolation of different density lipoproteins by ultracentrifugation can require lengthy centrifugation times and freeze/thawing of plasma may influence recovery. We isolated a range of lipoproteins using a preparative ultracentrifuge and the TLX micro-ultracentrifuge and determined the effect of freeze/thawing of plasma beforehand. In fresh plasma, there was no significant difference in results for small-dense low-density lipoprotein apolipoprotein B (LDL apoB) (density >1.044 g/mL) or cholesterol at density >1.006 g/mL. Freeze/thawing had no effect on closely correlated results for small-dense LDL apoB (r=0.85; pTLX micro-ultracentrifuge is a reliable alternative to the preparative ultracentrifuge and freeze/thawing has only a small effect on small-dense LDL apoB or high-density lipoprotein cholesterol.

  4. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Andrew L Carey

    Full Text Available BACKGROUND: Emerging evidence suggests that high density lipoprotein (HDL may modulate glucose metabolism through multiple mechanisms including pancreatic insulin secretion as well as insulin-independent glucose uptake into muscle. We hypothesized that HDL may also increase skeletal muscle insulin sensitivity via cholesterol removal and anti-inflammatory actions in macrophages associated with excess adiposity and ectopic lipid deposition. METHODS: Human primary and THP-1 macrophages were treated with vehicle (PBS or acetylated low density lipoprotein (acLDL with or without HDL for 18 hours. Treatments were then removed, and macrophages were incubated with fresh media for 4 hours. This conditioned media was then applied to primary human skeletal myotubes derived from vastus lateralis biopsies taken from patients with type 2 diabetes to examine insulin-stimulated glucose uptake. RESULTS: Conditioned media from acLDL-treated primary and THP-1 macrophages reduced insulin-stimulated glucose uptake in primary human skeletal myotubes compared with vehicle (primary macrophages, 168±21% of basal uptake to 104±19%; THP-1 macrophages, 142±8% of basal uptake to 108±6%; P<0.05. This was restored by co-treatment of macrophages with HDL. While acLDL increased total intracellular cholesterol content, phosphorylation of c-jun N-terminal kinase and secretion of pro- and anti-inflammatory cytokines from macrophages, none were altered by co-incubation with HDL. Insulin-stimulated Akt phosphorylation in human skeletal myotubes exposed to conditioned media was unaltered by either treatment condition. CONCLUSION: Inhibition of insulin-stimulated glucose uptake in primary human skeletal myotubes by conditioned media from macrophages pre-incubated with acLDL was restored by co-treatment with HDL. However, these actions were not linked to modulation of common pro- or anti-inflammatory mediators or insulin signaling via Akt.

  5. Inhibition of triacylglycerol and apoprotein B secretion and of low density lipoprotein binding in Hep G2 cells by eicosapentaenoic acid

    International Nuclear Information System (INIS)

    Wong, S.H.; Nestel, P.J.

    1987-01-01

    The consumption of long chain polyunsaturated fatty acids of fish oils leads to profound lowering of plasma triacylglyercol (TAG) but not of plasma cholesterol. Reasons for this were investigated with the human hepatoma cell line, the Hep G2 cell. Incubations with oleic acid (OA), linoleic acid (LA) and the characteristic marine fatty acid eicosapentaenoic acid (EPA) enriched cellular TAG mass, though least with EPA. However, secretion of very low density lipoprotein (VLDL)-TAG and apoprotein B (apo B), measured from [ 3 H]-glycerol and [ 3 H]-leucine was markedly inhibited by EPA. Preincubation with LA reduced VLDL-TAG but not apo B secretion in comparison with OA which stimulated both. A possible effect on low density lipoprotein (LDL) removal was studied by measuring [ 125 I]-LDL binding. Preincubation with either EPA or LA inhibited the saturable binding of LDL, observed with OA and control incubations. The binding of lipoproteins containing chylomicron remnants was not affected by any of the fatty acids

  6. Examination of the relation between periodontal health status and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen.

    Science.gov (United States)

    Wu, T; Trevisan, M; Genco, R J; Falkner, K L; Dorn, J P; Sempos, C T

    2000-02-01

    Using data from the Third National Health and Nutrition Examination Survey (1988-1994), the authors examined the relation between periodontal health and cardiovascular risk factors: serum total and high density lipoprotein cholesterol, C-reactive protein, and plasma fibrinogen. A total of 10,146 participants were included in the analyses of cholesterol and C-reactive protein and 4,461 in the analyses of fibrinogen. Periodontal health indicators included the gingival bleeding index, calculus index, and periodontal disease status (defined by pocket depth and attachment loss). While cholesterol and fibrinogen were analyzed as continuous variables, C-reactive protein was dichotomized into two levels. The results show a significant relation between indicators of poor periodontal status and increased C-reactive protein and fibrinogen. The association between periodontal status and total cholesterol level is much weaker. No consistent association between periodontal status and high density lipoprotein cholesterol was detectable. Similar patterns of association were observed for participants aged 17-54 years and those 55 years and older. In conclusion, this study suggests that total cholesterol, C-reactive protein, and fibrinogen are possible intermediate factors that may link periodontal disease to elevated cardiovascular risk.

  7. To Study the Activity of Paraoxonase-1 and High Density Lipoprotein-Cholesterol in Alcoholic Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Pooja Nemagoudar

    2017-01-01

    Full Text Available Background: Alcoholic liver cirrhosis is the most common complication of ethanol abuse. Alcoholic fatty liver progresses to alcoholic hepatitis, cirrhosis and liver failure. Lipoproteins are synthesized by the liver and secreted into the circulation. Alcoholic liver cirrhosis causes alteration in lipoprotein metabolism producing liver steatosis and necrosis. Paraoxonase-1 (PON-1 is an enzyme synthesized in liver and has an esterase activity towards lipid peroxides and circulates in plasma bound to High-Density Lipoproteins-cholesterol (HDL-c. Aim and Objectives: To determine the activity of PON-1 and levels of HDL-c in alcoholic liver disease and to correlate PON-1 activity with HDL-c. Materials and Methods: A Cross sectional study done in Department of Biochemistry and Department of Medicine, Belagavi Institute of Medical Sciences, Belagavi, Karnataka, India, from 1st December 2014 to 31st January 2016 Study included 50 males (age range 25-55 years with alcoholic liver cirrhosis and 50 healthy male participants (age range 25-55 years. PON-1 activity was estimated using spectrophotometric method by the hydrolysis of phenylacetate. HDL-c level was measured by cholesterol oxidase-peroxidase method. Results: The serum PON-1 activity and levels of HDL-c in patients with alcoholic liver cirrhosis were significantly reduced (p<0.001 compared with controls. Conclusion: A significant decrease in PON-1 and HDL-c in alcoholic liver cirrhosis may contribute to the risk of atherosclerosis in alcoholic liver cirrhosis patients.

  8. Macroporous poly(vinyl alcohol) microspheres bearing phosphate groups as a new adsorbent for low-density lipoprotein apheresis

    Energy Technology Data Exchange (ETDEWEB)

    Wang Weichao; Xie Hui; Ou Lailiang; Wang Lianyong; Yu Yaoting; Kong Deling [Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin 300071 (China); Sun Lisha, E-mail: wly@nankai.edu.c, E-mail: kongdeling@nankai.edu.c [General Hospital, Tianjin Medical University, Tianjin 300052 (China)

    2009-12-15

    A new low-density lipoprotein (LDL) adsorbent with phosphate groups as the ligand was prepared in this study. Macroporous poly(vinyl acetate-co-triallyl isocyanurate) microspheres were prepared using a free-radical suspension polymerization method. A hydrolysis reaction in sodium hydroxide/methanol changed the materials into poly(vinyl alcohol) (PVA) microspheres. Further reaction with phosphorus oxychloride in anhydrous DMF led to the LDL adsorbent PVA-phosphate microspheres. The preparation conditions such as reaction time, temperature and the amount of phosphorus oxychloride were optimized. The adsorption of plasma lipoproteins was examined by in vitro adsorption assays. The influence of adsorption time, plasma volume and ionic strength on the adsorption capacity was investigated. The circulation adsorption showed that the pathogenic lipoproteins in the plasma such as total cholesterol (TC), LDL and triglyceride (TG) could be removed markedly, in which the removal percentages were 42.9%, 45.0% and 44.74%, respectively. However, the reduction of high-density lipoprotein (HDL) and other normal plasma components was very slight. For in vivo experiment, rabbits were fed with high-cholesterol food to develop a hyperlipidemia model and treated by extracorporeal blood perfusion using the PVA-phosphate columns. Eight hyperlipidemia rabbits were treated with the PVA-phosphate adsorbent, and the removal of TC, LDL and TG was 45.03 +- 6.64%, 48.97 +- 9.92% and 35.42 +- 14.17%, respectively. The sterilization and storage tests showed that the adsorbent was chemically and functionally stable. It could be easily sterilized by a common method and stored for months without loss of adsorption capacity. Therefore, this new PVA-phosphate-based LDL adsorbent may have potential for application in LDL apheresis.

  9. Macroporous poly(vinyl alcohol) microspheres bearing phosphate groups as a new adsorbent for low-density lipoprotein apheresis

    International Nuclear Information System (INIS)

    Wang Weichao; Xie Hui; Ou Lailiang; Wang Lianyong; Yu Yaoting; Kong Deling; Sun Lisha

    2009-01-01

    A new low-density lipoprotein (LDL) adsorbent with phosphate groups as the ligand was prepared in this study. Macroporous poly(vinyl acetate-co-triallyl isocyanurate) microspheres were prepared using a free-radical suspension polymerization method. A hydrolysis reaction in sodium hydroxide/methanol changed the materials into poly(vinyl alcohol) (PVA) microspheres. Further reaction with phosphorus oxychloride in anhydrous DMF led to the LDL adsorbent PVA-phosphate microspheres. The preparation conditions such as reaction time, temperature and the amount of phosphorus oxychloride were optimized. The adsorption of plasma lipoproteins was examined by in vitro adsorption assays. The influence of adsorption time, plasma volume and ionic strength on the adsorption capacity was investigated. The circulation adsorption showed that the pathogenic lipoproteins in the plasma such as total cholesterol (TC), LDL and triglyceride (TG) could be removed markedly, in which the removal percentages were 42.9%, 45.0% and 44.74%, respectively. However, the reduction of high-density lipoprotein (HDL) and other normal plasma components was very slight. For in vivo experiment, rabbits were fed with high-cholesterol food to develop a hyperlipidemia model and treated by extracorporeal blood perfusion using the PVA-phosphate columns. Eight hyperlipidemia rabbits were treated with the PVA-phosphate adsorbent, and the removal of TC, LDL and TG was 45.03 ± 6.64%, 48.97 ± 9.92% and 35.42 ± 14.17%, respectively. The sterilization and storage tests showed that the adsorbent was chemically and functionally stable. It could be easily sterilized by a common method and stored for months without loss of adsorption capacity. Therefore, this new PVA-phosphate-based LDL adsorbent may have potential for application in LDL apheresis.

  10. Triglyceride to high-density lipoprotein cholesterol ratio and carotid intima-medial thickness in Chinese adolescents with newly diagnosed type 2 diabetes mellitus.

    Science.gov (United States)

    Li, Xin; Deng, You-Ping; Yang, Miao; Wu, Yu-Wen; Sun, Su-Xin; Sun, Jia-Zhong

    2016-03-01

    To investigate the relationship between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio and carotid intima-medial thickness (CIMT) in Chinese youth and adolescents with newly diagnosed type 2 diabetes mellitus (T2DM). Ninety-eight subjects aged 10-24 yr with newly-diagnosed T2DM had general inflammation, anthropometric, laboratory and CIMT data collected, and were divided into three groups based on TG/HDL-C tertiles. There were no significant differences in gender, age, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), and carotid arterial diameter (CAD) among the groups based on TG/HDL-C tertiles. Across TG/HDL-C tertiles, there was a significant progressive increase in body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), homeostasis model assessment-estimated insulin resistance (HOMA-IR), TG, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C) and CIMT (all P < 0.01 or P < 0.05), while HDL-C was decreased significantly across the groups (P < 0.01). In general linear regression model, TG/HDL-C was an independent determinant of CIMT even after adjusting for BMI, SBP, DBP, TG, TC, LDL-C, HDL-C, HbA1c and HOMA-IR. TG/HDL-C ratio, the marker of small dense LDL particles, is an independent determinant of CIMT in Chinese youth and adolescents with newly diagnosed T2DM, and may be a simple and helpful tool in predicting the increased CIMT in such patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Plasma cholesterol and related lipid levels of seemingly healthy ...

    African Journals Online (AJOL)

    The purpose of this study was achieved through analysis of fasting plasma samples for the following: Total cholesterol (TC), Triacylglycerols (TG), High density lipoprotein cholesterol (HDL), Low density lipoprotein cholesterol (LDL), and molar ratios of LDL/HDL, TC/ HDL, and TC/TG. Methods: One hundred and seventy four ...

  12. Quantitative studies of transfer in vivo of low density, Sf 12-60, and Sf 60-400 lipoproteins between plasma and arterial intima in humans

    International Nuclear Information System (INIS)

    Shaikh, M.; Wootton, R.; Nordestgaard, B.G.; Baskerville, P.; Lumley, J.S.; La Ville, A.E.; Quiney, J.; Lewis, B.

    1991-01-01

    To assess the potential of various plasma lipoprotein classes to contribute to the lipid content of the arterial intima, influx and efflux of these plasma lipoprotein fractions into and from the intima of human carotid arteries were measured in vivo. While low density lipoprotein (LDL) is known to transfer from plasma into the arterial wall, there is less information on the atherogenic potential of lipoproteins of intermediate density (Sf 12-60) or of very low density (Sf 60-400). Aliquots of the same lipoprotein (LDL, Sf 12-60 lipoprotein particles, or Sf 60-400 lipoprotein particles) iodinated with iodine-125 and iodine-131 were injected intravenously 18-29 hours and 3-6 hours, respectively, before elective surgical removal of atheromatous arterial tissue, and the intimal clearance of lipoproteins, lipoprotein influx, and fractional loss of newly entered lipoproteins were calculated. Intimal clearance of Sf 60-400 particles was not detectable (less than 0.3 microliter x hr-1 x cm-2), whereas the average value for both LDL and Sf 12-60 lipoprotein particles was 0.9 microliter x hr-1 x cm-2. Since the fractional loss of newly entered LDL and Sf 12-60 lipoprotein particles was also similar, the results suggest similar modes of entry and exit for these two particles. However, due to lower plasma concentrations of Sf 12-60 lipoproteins as compared with LDL, the mass influx of cholesterol in the Sf 12-60 particles was on the order of one 10th of that in LDL, and that of apolipoprotein B was about one 20th

  13. Native High Density Lipoproteins (HDL Interfere with Platelet Activation Induced by Oxidized Low Density Lipoproteins (OxLDL

    Directory of Open Access Journals (Sweden)

    Ivo Volf

    2013-05-01

    Full Text Available Platelets and lipoproteins play a crucial role in atherogenesis, in part by their ability to modulate inflammation and oxidative stress. While oxidized low density lipoproteins (OxLDL play a central role in the development of this disease, high density lipoproteins (HDL represent an atheroprotective factor of utmost importance. As platelet function is remarkably sensitive to the influence of plasma lipoproteins, it was the aim of this study to clarify if HDL are able to counteract the stimulating effects of OxLDL with special emphasis on aspects of platelet function that are relevant to inflammation. Therefore, HDL were tested for their ability to interfere with pro-thrombotic and pro-inflammatory aspects of platelet function. We are able to show that HDL significantly impaired OxLDL-induced platelet aggregation and adhesion. In gel-filtered platelets, HDL decreased both the formation of reactive oxygen species and CD40L expression. Furthermore, HDL strongly interfered with OxLDL-induced formation of platelet-neutrophil aggregates in whole blood, suggesting that platelets represent a relevant and sensitive target for HDL. The finding that HDL effectively competed with the binding of OxLDL to the platelet surface might contribute to their atheroprotective and antithrombotic properties.

  14. Recombinant high-density lipoprotein nanoparticles containing gadolinium-labeled cholesterol for morphologic and functional magnetic resonance imaging of the liver

    Directory of Open Access Journals (Sweden)

    Rui M

    2012-07-01

    Full Text Available Mengjie Rui,1 Wei Guo,2 Qian Ding,2 Xiaohui Wei,2 Jianrong Xu,3 Yuhong Xu21School of Life Science and Biotechnology, 2School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China; 3Department of Radiology, Renji Hospital Affiliation with Medical School of Shanghai Jiao Tong University, Shanghai, People's Republic of ChinaBackground: Natural high-density lipoproteins (HDL possess important physiological functions to the transport of cholesterol from the peripheral tissues to the liver for metabolic degradation and excretion in the bile.Methods and results: In this work, we took advantage of this pathway and prepared two different gadolinium (Gd-DTPA-labeled cholesterol-containing recombinant HDL nanoparticles (Gd-chol-HDL and Gd-(chol2-HDL as liver-specific magnetic resonance imaging (MRI contrast agents. The reconstituted HDL nanoparticles had structural similarity to native HDL, and could be taken up by HepG2 cells via interaction with HDL receptors in vitro. In vivo MRI studies in rats after intravenous injections of 10 µmol gadolinium per kg of recombinant HDL nanoparticles indicated that both nanoparticles could provide signal enhancement in the liver and related organs. However, different T1-weighted image details suggested that they participated in different cholesterol metabolism and excretion pathways in the liver.Conclusion: Such information could be highly useful to differentiate functional changes as well as anatomic differences in the liver. These cholesterol-derived contrast agents and their recombinant HDL preparations may warrant further development as a new class of contrast agents for MRI of the liver and related organs.Keywords: magnetic resonance imaging, apolipoprotein, high-density lipoprotein, contrast agent, gadolinium, liver

  15. Correlation between serum lipoproteins and abdominal fat pad in ...

    African Journals Online (AJOL)

    GREGORY

    2010-08-30

    Aug 30, 2010 ... Triglyceride, cholesterol and VLDL concentrations were positively correlated with ... negative correlation was observed between high-density lipoprotein and ... Abbreviations: HDL, High density lipoprotein; VLDL, very low.

  16. Niacin to Boost Your HDL "Good" Cholesterol

    Science.gov (United States)

    Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

  17. Role of oxidized low-density lipoprotein in renal disease

    NARCIS (Netherlands)

    Heeringa, P; Tervaert, JWC

    Accelerated atherosclerosis is often observed in patients with chronic renal failure. In the present review we summarize and discuss the recent literature on the pathogenic role of low-density lipoproteins modified by oxidative processes in atherosclerosis and the possible role in renal diseases.

  18. Human Low Density Lipoprotein as a Vehicle of Atherosclerosis ...

    African Journals Online (AJOL)

    Low-density lipoproteins have been sufficiently established as an important precursor of atherosclerosis. The actual mechanism is still unclear, and the current technique of using radioisotopes has clinical limitation. However, the current study techniques or methods excellently elucidate the functional aspects of ...

  19. [Consensus on objectives and action guidelines on low density lipoproteins-cholesterol control in very high risk cardiovascular patients].

    Science.gov (United States)

    Galve, Enrique; Guijarro-Herraiz, Carlos; Masana-Marin, Luis; Cordero-Fort, Alberto

    2016-01-01

    Cardiovascular disease is the leading cause of death in developed countries. Among cardiovascular disease risk factors one of the most relevant is low-density lipoprotein-associated cholesterol (LDL-c), but there is controversy about the methods used to control it. The aim was to obtain an expert opinion to clarify the most relevant issues regarding the control of dyslipidemia in very high cardiovascular risk patients. A survey with 55 items, stratified into 4 blocks: LDL-c as a therapeutic target, therapeutic goals, causes of the failure to achieve LDL-c goals, and recommendations to optimize their achievement, was addressed to 41 specialists (Cardiology and Internal Medicine) using the Delphi method to achieve professional consensus criteria. A high consensus was reached among all items, in line with the European recommendations. The panelists considered that the goal of 70mg/dl for LDL-c for high cardiovascular disease risk (mainly vascular disease, diabetes mellitus, and renal failure), using combined treatment when necessary. Lack of adherence and therapeutic inertia were considered the main reasons for treatment failure. The Spanish experts show an elevated consensus with the European recommendations, confirming the LDL-c control target of <70mg/dl. The simplification of the guidelines and the combined treatment may favor an improvement the achievement of lipid target goals. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  20. Additional consumption of one egg per day increases serum lutein plus zeaxanthin concentration and lowers oxidized low-density lipoprotein in moderately hypercholesterolemic males.

    Science.gov (United States)

    Kishimoto, Yoshimi; Taguchi, Chie; Saita, Emi; Suzuki-Sugihara, Norie; Nishiyama, Hiroshi; Wang, Wei; Masuda, Yasunobu; Kondo, Kazuo

    2017-09-01

    The egg is a nutrient-dense food and contains antioxidative carotenoids, lutein and zeaxanthin, but its impact on serum cholesterol levels has been a matter of concern, especially for individuals who have high serum cholesterol levels. We conducted this study to determine whether and how the daily additional consumption of one egg affects serum lipid profiles and parameters of LDL oxidation in moderately hypercholesterolemic males. Nineteen male Japanese adults (total cholesterol [TC]>5.2mmol/L) participated, consuming one soft boiled egg per day for 4weeks in addition to their habitual diet. Despite the significant increase in their intake of dietary cholesterol during the intervention period, the subjects' serum concentrations of TC and low-density lipoprotein cholesterol (LDL-C) did not increase. Their serum malondialdehyde modified low-density lipoprotein (MDA-LDL) concentrations were significantly decreased and their LDL oxidation lag times, reflecting the resistance of free-radical-induced LDL lipid peroxidation (ex vivo), was prolonged after 2 and 4weeks. At weeks 2 and 4, the subjects' serum lutein+zeaxanthin concentrations were significantly higher than their baseline values and showed both an inverse relation with MDA-LDL and a positive relationship with the LDL oxidation lag time. These data showed that in moderately hypercholesterolemic males, the additional consumption of one egg per day for 4weeks did not have adverse effects on serum TC or LDL-C, and it might reduce the susceptibility of LDL to oxidation through an increase in the serum lutein and zeaxanthin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. PCSK9 R46L Loss-of-Function Mutation Reduces Lipoprotein(a), LDL Cholesterol, and Risk of Aortic Valve Stenosis

    DEFF Research Database (Denmark)

    Langsted, Anne; Nordestgaard, Børge; Benn, Marianne

    2016-01-01

    CONTEXT: Novel, low-density lipoprotein (LDL) cholesterol-lowering proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors also lower lipoprotein(a) levels, but the effect on aortic valve stenosis and myocardial infarction is unknown. OBJECTIVE: We tested the hypothesis that the PCSK9 R46L...... individuals of Danish descent. PARTICIPANTS: We studied 103 083 individuals from the Copenhagen General Population Study, the Copenhagen City Heart Study, and the Copenhagen Ischemic Heart Disease Study. MAIN OUTCOME MEASURES: Lipoprotein(a), LDL cholesterol, and PCSK9 R46L genotype and diagnoses of aortic...... P = .02). The corresponding values for LDL cholesterol levels were 124 (101-147) mg/dl, 104 (85-132) mg/dl, and 97 (85-128) mg/dl, respectively (trend P = 2 × 10(-52)). PCSK9 R46L carriers vs noncarriers had an age- and sex-adjusted odds ratio of 0.64 (95% confidence interval, 0.44-0.95) for aortic...

  2. Extract of mangosteen increases high density lipoprotein levels in rats fed high lipid

    Directory of Open Access Journals (Sweden)

    Dwi Laksono Adiputro

    2013-04-01

    Full Text Available Background In cardiovascular medicine, Garcinia mangostana has been used as an antioxidant to inhibit oxidation of low density lipoproteins and as an antiobesity agent. The effect of Garcinia mangostana on hyperlipidemia is unknown. The aim of this study was to evaluate the effect of an ethanolic extract of Garcinia mangostana pericarp on lipid profile in rats fed a high lipid diet. Methods A total of 40 rats were divided into five groups control, high lipid diet, and high lipid diet + ethanolic extract of Garcinia mangostana pericarp at dosages of 200, 400, and 800 mg/kg body weight. The control group received a standard diet for 60 days. The high lipid diet group received standard diet plus egg yolk, goat fat, cholic acid, and pig fat for 60 days with or without ethanolic extract of Garcinia mangostana pericarp by the oral route. After 60 days, rats were anesthesized with ether for collection of blood by cardiac puncture. Analysis of blood lipid profile comprised colorimetric determination of cholesterol, triglyceride, low density lipoprotein (LDL, and high density lipoprotein (HDL. Results From the results of one-way ANOVA it was concluded that there were significant between-group differences in cholesterol, trygliceride, LDL, and HDL levels (p=0.000. Ethanolic extract of Garcinia mangostana pericarp significantly decreased cholesterol, trygliceride, and LDL levels, starting at 400 mg/kg body weight (p=0.000. Ethanolic extract of Garcinia mangostana pericarp significantly increased HDL level starting at 200 mg/kg body weight (p=0.000. Conclusion Ethanolic extract of Garcinia mangostana pericarp has a beneficial effect on lipid profile in rats on a high lipid diet.

  3. Extract of mangosteen increases high density lipoprotein levels in rats fed high lipid

    Directory of Open Access Journals (Sweden)

    Dwi Laksono Adiputro

    2015-12-01

    Full Text Available BACKGROUND In cardiovascular medicine, Garcinia mangostana has been used as an antioxidant to inhibit oxidation of low density lipoproteins and as an antiobesity agent. The effect of Garcinia mangostana on hyperlipidemia is unknown. The aim of this study was to evaluate the effect of an ethanolic extract of Garcinia mangostana pericarp on lipid profile in rats fed a high lipid diet. METHODS A total of 40 rats were divided into five groups control, high lipid diet, and high lipid diet + ethanolic extract of Garcinia mangostana pericarp at dosages of 200, 400, and 800 mg/kg body weight. The control group received a standard diet for 60 days. The high lipid diet group received standard diet plus egg yolk, goat fat, cholic acid, and pig fat for 60 days with or without ethanolic extract of Garcinia mangostana pericarp by the oral route. After 60 days, rats were anesthesized with ether for collection of blood by cardiac puncture. Analysis of blood lipid profile comprised colorimetric determination of cholesterol, triglyceride, low density lipoprotein (LDL, and high density lipoprotein (HDL. RESULTS From the results of one-way ANOVA it was concluded that there were significant between-group differences in cholesterol, trygliceride, LDL, and HDL levels (p=0.000. Ethanolic extract of Garcinia mangostana pericarp significantly decreased cholesterol, trygliceride, and LDL levels, starting at 400 mg/kg body weight (p=0.000. Ethanolic extract of Garcinia mangostana pericarp significantly increased HDL level starting at 200 mg/kg body weight (p=0.000. CONCLUSION Ethanolic extract of Garcinia mangostana pericarp has a beneficial effect on lipid profile in rats on a high lipid diet.

  4. In vitro biological efficacy of boronated low density lipoproteins for NCT

    International Nuclear Information System (INIS)

    Kahl, S.B.; Pate, D.; Laster, B.H.; Popenoe, E.A.; Fairchild, R.G.

    1992-01-01

    Low Density Lipoproteins (LDLs) are known to be internalized within the cell by receptor-mediated mechanisms. There is evidence that LDLs may be taken up avidly by tumor cells to provide cholesterol for the synthesis of cell membrane. Thus, the possibility exists that LDLs may provide an ideal vehicle for the transport of boron to tumor cells for Neutron Capture Therapy (NCT). A boronated analog of LDL has recently been synthesized for possible application in NCT. The analog was tested in cell culture for uptake and biological efficacy in the thermal neutron beam at the Brookhaven Medical Research Reactor (BMRR). It was found that boron concentrations ten times higher than that required for NCT were easily obtained, and that uptake data were constant with a receptor mediated binding mechanism. The measured intracellular concentration of ∼240 μg 10 B/g cells is significantly higher than that obtained with any other boron compound previously evaluated for possible clinical application

  5. Non-high-density lipoprotein cholesterol on the risks of stroke: a result from the Kailuan study.

    Directory of Open Access Journals (Sweden)

    Jianwei Wu

    Full Text Available AIMS: To prospectively explore the association between non-high-density lipoprotein cholesterol (non-HDLC and the risks of stroke and its subtypes. METHODS: A total of 95,916 participants (18-98 years old; 76,354 men and 19,562 women from a Chinese urban community who were free of myocardial infarction and stroke at baseline time point (2006-2007 were eligible and enrolled in the study. The serum non-HDLC levels of participants were determined by subtracting the high-density lipoprotein cholesterol (HDLC from total serum cholesterol. The primary outcome was the first occurrence of stroke, which was diagnosed according to the World Health Organization criteria and classified into three subtypes: ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. The Cox proportional hazards models were used to estimate risk of stroke and its subtypes. RESULTS: During the four-year follow-up, we identified 1614 stroke events (1,156 ischemic, 416 intracerebral hemorrhagic and 42 subarachnoid hemorrhagic. Statistical analyses showed that hazard ratios (HR (95% Confidence Interval: CI of serum Non-HDLC level for total and subtypes of stroke were: 1.08 (1.03-1.12 (total, 1.10 (1.05-1.16 (ischemic, 1.03 (0.96-1.10 (intracerebral hemorrhage and 0.83 (0.66-1.05 (subarachnoid hemorrhage. HR for non-HDLC refers to the increase per each 20 mg/dl. For total and ischemic stroke, the risks were significantly higher in the fourth and fifth quintiles of non-HDLC concentrations compared to the first quintile after adjusting the confounding factors (total stroke: 4(th quintile HR=1.33 (1.12-1.59; 5(th quintile HR = 1.36 (1.15-1.62; ischemic stroke: 4(th quintile HR =1.34 (1.09-1.66; 5(th quintile HR = 1.53 (1.24-1.88. CONCLUSIONS: Our data suggest that serum non-HDLC level is an independent risk factor for total and ischemic stroke, and that higher serum non-HDLC concentrations are associated with increased risks for total stroke and ischemic stroke, but not

  6. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    International Nuclear Information System (INIS)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J.

    2014-01-01

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL

  7. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J., E-mail: rbrown@mun.ca

    2014-09-05

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  8. Association of triglyceride-rich lipoproteins-related markers and low-density lipoprotein heterogeneity with cardiovascular risk: effectiveness of polyacrylamide-gel electrophoresis as a method of determining low-density lipoprotein particle size.

    Science.gov (United States)

    Tani, Shigemasa; Matsumoto, Michiaki; Nagao, Ken; Hirayama, Atsushi

    2014-01-01

    Despite well-controlled low-density lipoprotein cholesterol (LDL-C), hypertriglyceridemia is an independent predictor of coronary events. We investigated the risk of atherosclerotic cardiovascular disease through examining the relation between triglyceride (TG) metabolism and LDL-heterogeneity as assessed by polyacrylamide-gel electrophoresis (PAGE). Estimated LDL-particle size [relative LDL migration (LDL-Rm value)] measured by PAGE with the LipoPhor system (Joko, Tokyo, Japan) was evaluated in 645 consecutive patients with one additional risk factor for atherosclerotic cardiovascular disease.Multivariate regression analysis after adjustments for traditional risk factors revealed an elevated triglyceride-rich lipoproteins (TRLs)-related markers [TG, remnant-like particle cholesterol (RLP-C), very LDL (VLDL) fraction, apolipoprotein (apo) C-II, and apo C-III] level to be an independent predictor of smaller-size LDL-particle size, both in the overall population, and in a subset of patients with serum LDL-C <100 mg/dL. Even among the patients with LDL-C levels <100 mg/dL, the serum levels of atherogenic lipid markers in those with a LDL-Rm value ≥0.40, suggesting the presence of large amounts of small-dense LDL and upper limit (mean+2 standard deviation) in this population, were significantly higher than in those with a LDL-Rm value <0.40. Moreover, the serum levels of TRLs-related markers showed high accurate area under the receiver-operating characteristic curve (TG, 0.896; RLP-C, 0.875; VLDL fraction, 0.803; apo C-II, 0.778; and apo C-III, 0.804, respectively) in terms of evaluation of the indicators of LDL-Rm value ≥0.40. To further reduce the risk of atherosclerotic cardiovascular disease, it may be of particular importance to pay attention not only to the quantitative change in the serum LDL-C, but also TG-metabolism associated with LDL-heterogeneity. Combined evaluation of TRLs-related markers and LDL-Rm value may be useful for assessing the risk of

  9. Lp(a-cholesterol is associated with HDL-cholesterol in overweight and obese African American children and is not an independent risk factor for CVD

    Directory of Open Access Journals (Sweden)

    Sharma Sushma

    2012-01-01

    Full Text Available Abstract Background The role of Lipoprotein (a cholesterol {Lp(a-C}as an additional and/or independent risk factor for cardiovascular disease (CVD is not clear. We evaluated the associations between Lp(a-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children. Methods A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with Body Mass Index (BMI's greater than the 85th percentile. Body height, weight and waist circumference (WC were measured. Fasting plasma concentrations of Lp(a-C, Total cholesterol (TC, High density lipoprotein cholesterol (HDL-C, Very low density lipoprotein cholesterol (VLDL-C, Intermediate density lipoprotein cholesterol (IDL-C, Low density lipoprotein cholesterol (LDL-C, and Triacylglycerides (TAG were analyzed using the vertical auto profile (VAP cholesterol method. Results After adjusting for child age, gender, and pubertal status, Lp(a-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a-C remained strongly associated with HDL-C, whereas the associations of Lp(a-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models. Conclusions Lp(a-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a cholesterol is not an independent risk factor for CVD in African American children.

  10. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Peng, Shi-Kaung; Phillips, G.A.; Xia, Guang-Zhi; Morin, R.J.

    1987-01-01

    Radiolabeled pure [4- 14 C] cholesterol was kept at 60 0 C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  11. Low density lipoprotein receptor gene Ava II polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    Directory of Open Access Journals (Sweden)

    Wu Dong-Feng

    2011-02-01

    Full Text Available Abstract Background Several common genetic polymorphisms in the low density lipoprotein receptor (LDL-R gene have associated with modifications of serum total cholesterol (TC and low density lipoprotein cholesterol (LDL-C levels, but the results are not consistent in different populations. Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 1024 subjects of Bai Ku Yao and 792 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LDL-R gene Ava Ⅱ polymorphism was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results The levels of serum TC, high density lipoprotein cholesterol (HDL-C, LDL-C, apolipoprotein (Apo A1 and the ratio of ApoA1 to ApoB were lower in Bai Ku Yao than in Han (P - and A+ alleles was 65.5% and 34.5% in Bai Ku Yao, and 80.7% and 19.3% in Han (P -A-, A-A+ and A+A+ genotypes was 42.6%, 45.9% and 11.5% in Bai Ku Yao, and 64.9%, 31.6% and 3.5% in Han (P P 3.20 mmol/L subgroups in Bai Ku Yao (P P P P +A+ genotype had higher serum LDL-C, TC, HDL-C or ApoA1 levels than the subjects with A-A+ and A-A- genotypes. Spearman rank correlation analysis revealed that the levels of LDL-C in Bai Ku Yao and HDL-C in Han were correlated with genotypes (P P Conclusions The association of LDL-R gene Ava Ⅱ polymorphism and serum lipid levels is different between the Bai Ku Yao and Han populations. The discrepancy might partly result from different LDL-R gene Ava Ⅱ polymorphism or LDL-R gene-enviromental interactions.

  12. Hepatitis C Virus, Cholesterol and Lipoproteins — Impact for the Viral Life Cycle and Pathogenesis of Liver Disease

    Science.gov (United States)

    Felmlee, Daniel J.; Hafirassou, Mohamed Lamine; Lefevre, Mathieu; Baumert, Thomas F.; Schuster, Catherine

    2013-01-01

    Hepatitis C virus (HCV) is a leading cause of chronic liver disease, including chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Hepatitis C infection associates with lipid and lipoprotein metabolism disorders such as hepatic steatosis, hypobetalipoproteinemia, and hypocholesterolemia. Furthermore, virus production is dependent on hepatic very-low-density lipoprotein (VLDL) assembly, and circulating virions are physically associated with lipoproteins in complexes termed lipoviral particles. Evidence has indicated several functional roles for the formation of these complexes, including co-opting of lipoprotein receptors for attachment and entry, concealing epitopes to facilitate immune escape, and hijacking host factors for HCV maturation and secretion. Here, we review the evidence surrounding pathogenesis of the hepatitis C infection regarding lipoprotein engagement, cholesterol and triglyceride regulation, and the molecular mechanisms underlying these effects. PMID:23698400

  13. Impact of the Triglyceride/High-Density Lipoprotein Cholesterol Ratio and the Hypertriglyceremic-Waist Phenotype to Predict the Metabolic Syndrome and Insulin Resistance.

    Science.gov (United States)

    von Bibra, Helene; Saha, Sarama; Hapfelmeier, Alexander; Müller, Gabriele; Schwarz, Peter E H

    2017-07-01

    Insulin resistance is the underlying mechanism for the metabolic syndrome and associated dyslipidaemia that theoretically implies a practical tool for identifying individuals at risk for cardiovascular disease and type-2-diabetes. Another screening tool is the hypertriglyceremic-waist phenotype (HTW). There is important impact of the ethnic background but a lack of studied European populations for the association of the triglyceride/high-density lipoprotein cholesterol (HDL-C) ratio and insulin resistance. This observational, retrospective study evaluated lipid ratios and the HTW for predicting the metabolic syndrome/insulin resistance in 1932 non-diabetic individuals from Germany in the fasting state and during a glucose tolerance test. The relations of triglyceride/HDL-C, total-cholesterol/HDL-C, and low-density lipoprotein cholesterol/HDL-C with 5 surrogate estimates of insulin resistance/sensitivity and metabolic syndrome were analysed by linear regression analysis and receiver operating characteristics (ROC) in participants with normal (n=1 333) or impaired fasting glucose (n=599), also for the impact of gender. Within the lipid ratios, triglyceride/HDL-C had the strongest associations with insulin resistance/sensitivity markers. In the prediction of metabolic syndrome, diagnostic accuracy was good for triglyceride/HDL-C (area under the ROC curve 0.817) with optimal cut-off points (in mg/dl units) of 2.8 for men (80% sensitivity, 71% specificity) and 1.9 for women (80% sensitivity, 75% specificity) and fair for HTW and HOMA-IR (area under the curve 0.773 and 0.761). These data suggest the triglyceride/HDL-C ratio as a physiologically relevant and practical index for predicting the concomitant presence of metabolic syndrome, insulin resistance and dyslipidaemia for therapeutic and preventive care in apparently healthy European populations. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Relations Between Atherogenic Index of Plasma, Ratio of Small Dense Low Density Lipoprotein/Lecithin Cholesterol Acyl Transferase and Ratio of Small Dense Low Density Lipoprotein/Cholesteryl Ester Transfer Protein of Controlled and Uncontrolled Type 2 DM

    Directory of Open Access Journals (Sweden)

    Ellis Susanti

    2009-08-01

    Full Text Available BACKGROUND: Patients with Diabetes Melitus are proven to be prone to atherosclerosis and coronary heart disease, especially type 2 Diabetes Melitus (T2DM patient who have higher risk and mortality for cardiovascular risk factor. The Dyslipidemia condition is very common in T2DM as one of the risk factors. Diabetic dyslipidemia is marked by the increased triglyceride (TG, low HDL cholesterol (HDL-C, and increased small dense LDL and apolipoprotein B. Therefore the aim of this study is to assess the differential and correlation between Atherogenic Index of Plasma (AIP, ratio of small dense low density lipoprotein (sdLDL/lecithin cholesterol acyl transferase (LCAT and ratio of sdLDL/cholesteryl ester transfer protein (CETP of controlled and uncontrolled T2DM. METHODS: This study was observational with cross sectional design. In total of 72 patients with T2DM consist of 36 controlled and 36 uncontrolled, participated in this study. The serum TG, HDL-C, sdLDL, LCAT and CETP were examined in their relationship with to T2DM risk. RESULTS: The results of the study indicate that the AIP (p<0.001 increase controlled and uncontrolled T2DM and the ratio of sdLDL/CETP (p=0.004, odds ratio of AIP was 4 (95% CI: 1.501-10.658 and odds ratio of sdLDL/CETP ratio was 4 (95% CI: 1.501-10.658 in uncontrolled T2DM. CONCLUSIONS: This study showed that the AIP and ratio of small dense LDL/CETP had a significant correlation with the uncontrolled T2DM. The AIP and ratio of small dense LDL/CETP increase was found at the uncontrolled T2DM to be 4 times greater than the controlled T2DM. KEYWORDS: T2DM, atherosclerosis, atherogenic index of plasma, small dense LDL, LCAT, CETP, ratio of sdLDL/LCAT, ratio of sdLDL/CETP.

  15. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    DEFF Research Database (Denmark)

    Postmus, Iris; Warren, Helen R; Trompet, Stella

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed...... a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p

  16. High density lipoproteins, dyslipidemia, and coronary heart disease

    National Research Council Canada - National Science Library

    2010-01-01

    ... with premature coronary heart disease (CHD). These familial disorders include lipoprotein(a) excess, dyslipidemia (high triglycerides and low HDL), combined hyperlipidemia (high cholesterol and high triglycerides often with low HDL), hypoalphalipoproteinemia (low HDL), and hypercholesterolemia. We discuss the management of these disorders. W...

  17. Development and partial metabolic characterization of a dietary cholesterol-resistant colony of rabbits

    International Nuclear Information System (INIS)

    Overturf, M.L.; Smith, S.A.; Hewett-Emmett, D.; Loose-Mitchell, D.S.; Soma, M.R.; Gotto, A.M. Jr.; Morrisett, J.D.

    1989-01-01

    A colony of New Zealand white rabbits has been developed which, when fed a cholesterol-supplemented diet, exhibit unusual resistance to hypercholesterolemia and atherosclerosis, disorders usually observed in normal cholesterol-fed rabbits. When resistant rabbits (RT) were fed a normal low cholesterol diet (ND), their plasma lipoprotein patterns were significantly different from those of normal rabbits (NR) fed the same diet. The low density lipoprotein cholesterol (LDL-c)/high density lipoprotein cholesterol (HDL-c) ratio and LDL-c/very low density lipoprotein cholesterol (VLDL-c) ratio were lower in the resistant rabbits. The hydrated density of HDL of the normal-responsive rabbits was greater than that of the resistant rabbits. LDL from resistant rabbits contained a lower proportion of esterified cholesterol and protein than LDL from normal rabbits. Peripheral mononuclear cells from resistant rabbits bound about 30% more 125 I-labeled rabbit LDL than mononuclear cells from normal rabbits. These results demonstrate that the plasma cholesterol levels of these animals is at least partly under genetic control and that compositional differences exist between the major plasma lipoprotein classes of normal and resistant rabbits even during the ingestion of low-cholesterol diet. The results indicate that at least a part of the difference in the cholesterolemic responses between the two rabbit groups is due to an enhanced LDL uptake by the mononuclear cells, and presumably by other somatic cells of the resistant group

  18. Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

    NARCIS (Netherlands)

    Sjouke, B.; Yahya, R.; Tanck, M.W.T.; Defesche, J.C.; Graaf, J. de; Wiegman, A.; Kastelein, J.J.; Mulder, M.T.; Hovingh, G.K.; Roeters van Lennep, J.E.

    2017-01-01

    BACKGROUND: Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and

  19. Whole-exome sequencing identifies rare and low-frequency coding variants associated with LDL cholesterol

    NARCIS (Netherlands)

    L.A. Lange (Leslie); Y. Hu (Youna); H. Zhang (He); C. Xue (Chenyi); E.M. Schmidt (Ellen); Z.-Z. Tang (Zheng-Zheng); C. Bizon (Chris); E.M. Lange (Ethan); G.D. Smith; E.H. Turner (Emily); Y. Jun (Yang); H.M. Kang (Hyun Min); G.M. Peloso (Gina); P. Auer (Paul); K.-P. Li (Kuo-Ping); J. Flannick (Jason); J. Zhang (Ji); C. Fuchsberger (Christian); K. Gaulton (Kyle); C.M. Lindgren (Cecilia); A. Locke (Adam); A.K. Manning (Alisa); X. Sim (Xueling); M.A. Rivas (Manuel); O.L. Holmen (Oddgeir); R.F. Gottesman (Rebecca); Y. Lu (Yingchang); D. Ruderfer (Douglas); E.A. Stahl (Eli); Q. Duan (Qing); Y. Li (Yun); P. Durda (Peter); S. Jiao (Shuo); A.J. Isaacs (Aaron); A. Hofman (Albert); J.C. Bis (Joshua); D.D. Correa; M.D. Griswold (Michael); M. Jakobsdottir (Margret); G.D. Smith; P.J. Schreiner (Pamela); M.F. Feitosa (Mary Furlan); Q. Zhang (Qunyuan); J.E. Huffman (Jennifer); S. Crosby; C.L. Wassel (Christina); R. Do (Ron); N. Franceschini (Nora); L.W. Martin (Lisa); J.G. Robinson (Jennifer); T.L. Assimes (Themistocles); D.R. Crosslin (David); E.A. Rosenthal (Elisabeth); M.Y. Tsai (Michael); M. Rieder (Mark); D.N. Farlow (Deborah); A.R. Folsom (Aaron); T. Lumley (Thomas); E.R. Fox (Ervin); C.S. Carlson (Christopher); U. Peters (Ulrike); R.D. Jackson (Rebecca); C.M. van Duijn (Cornelia); A.G. Uitterlinden (André); D. Levy (Daniel); J.I. Rotter (Jerome); H.A. Taylor (Herman); V. Gudnason (Vilmundur); D.S. Siscovick (David); M. Fornage (Myriam); I.B. Borecki (Ingrid); C. Hayward (Caroline); I. Rudan (Igor); Y.E. Chen (Y. Eugene); E.P. Bottinger (Erwin); R.J.F. Loos (Ruth); P. Sætrom (Pål); K. Hveem (Kristian); M. Boehnke (Michael); L. Groop (Leif); M.I. McCarthy (Mark); T. Meitinger (Thomas); C. Ballantyne (Christie); S.B. Gabriel (Stacey); C.J. O'Donnell (Christopher); W.S. Post (Wendy S.); K.E. North (Kari); A. Reiner (Alexander); E.A. Boerwinkle (Eric); B.M. Psaty (Bruce); D. Altshuler (David); S. Kathiresan (Sekar); D.Y. Lin (Dan); G.P. Jarvik (Gail); L.A. Cupples (Adrienne); C. Kooperberg (Charles); J.G. Wilson (James); D.A. Nickerson (Deborah); G.R. Abecasis (Gonçalo); S.S. Rich (Stephen); R.P. Tracy (Russell); C.J. Willer (Cristen)

    2014-01-01

    textabstractElevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency

  20. Plasma lipoprotein(a) levels in patients with homozygous autosomal dominant hypercholesterolemia

    NARCIS (Netherlands)

    Sjouke, Barbara; Yahya, Reyhana; Tanck, Michael W. T.; Defesche, Joep C.; de Graaf, Jacqueline; Wiegman, Albert; Kastelein, John J. P.; Mulder, Monique T.; Hovingh, G. Kees; Roeters van Lennep, Jeanine E.

    2017-01-01

    Patients with autosomal dominant hypercholesterolemia (ADH), caused by mutations in either low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), or proprotein convertase subtilisin-kexin type 9 (PCSK9) are characterized by high low-density lipoprotein cholesterol levels and in some

  1. Novel lipoprotein density profiling in healthy dogs of various breeds, healthy miniature schnauzers, and miniature schnauzers with hyperlipidemia

    Science.gov (United States)

    2013-01-01

    Background Despite the importance of abnormalities in lipoprotein metabolism in clinical canine medicine, the fact that most previously used methods for lipoprotein profiling are rather laborious and time-consuming has been a major obstacle to the wide clinical application and use of lipoprotein profiling in this species. The aim of the present study was to assess the feasibility of a continuous lipoprotein density profile (CLPDP) generated within a bismuth sodium ethylenediaminetetraacetic acid (NaBiEDTA) density gradient to characterize and compare the lipoprotein profiles of healthy dogs of various breeds, healthy Miniature Schnauzers, and Miniature Schnauzers with primary hypertriacylglycerolemia. A total of 35 healthy dogs of various breeds with serum triacylglycerol (TAG) and cholesterol concentrations within their respective reference intervals were selected for use as a reference population. Thirty-one Miniature Schnauzers with serum TAG and cholesterol concentrations within their respective reference intervals and 31 Miniature Schnauzers with hypertriacylglyceridemia were also included in the study. Results The results suggest that CLPDP using NaBiEDTA provides unique diagnostic information in addition to measurements of serum TAG and cholesterol concentrations and that it is a useful screening method for dogs with suspected lipoprotein metabolism disorders. Using the detailed and continuous density distribution information provided by the CLPDP, important differences in lipoprotein profiles can be detected even among dogs that have serum TAG and cholesterol concentrations within the reference interval. Miniature Schnauzers with serum TAG and cholesterol concentrations within the reference interval had significantly different lipoprotein profiles than dogs of various other breeds. In addition, it was further established that specific lipoprotein fractions are associated with hypertriacylglyceridemia in Miniature Schnauzers. Conclusions The results of the

  2. Protective effect of the silkworm protein 30Kc6 on human vascular endothelial cells damaged by oxidized low density lipoprotein (Ox-LDL.

    Directory of Open Access Journals (Sweden)

    Wei Yu

    Full Text Available Although the 30K family proteins are important anti-apoptotic molecules in silkworm hemolymph, the underlying mechanism remains to be investigated. This is especially the case in human vascular endothelial cells (HUVECs. In this study, a 30K protein, 30Kc6, was successfully expressed and purified using the Bac-to-Bac baculovirus expression system in silkworm cells. Furthermore, the 30Kc6 expressed in Escherichia coli was used to generate a polyclonal antibody. Western blot analysis revealed that the antibody could react specifically with the purified 30Kc6 expressed in silkworm cells. The In vitro cell apoptosis model of HUVEC that was induced by oxidized low density lipoprotein (Ox-LDL and in vivo atherosclerosis rabbit model were constructed and were employed to analyze the protective effects of the silkworm protein 30Kc6 on these models. The results demonstrated that the silkworm protein 30Kc6 significantly enhanced the cell viability in HUVEC cells treated with Ox-LDL, decreased the degree of DNA fragmentation and markedly reduced the level of 8-isoprostane. This could be indicative of the silkworm protein 30Kc6 antagonizing the Ox-LDL-induced cell apoptosis by inhibiting the intracellular reactive oxygen species (ROS generation. Furthermore, Ox-LDL activated the cell mitogen activated protein kinases (MAPK, especially JNK and p38. As demonstrated with Western analysis, 30Kc6 inhibited Ox-LDL-induced cell apoptosis in HUVEC cells by preventing the MAPK signaling pathways. In vivo data have demonstrated that oral feeding of the silkworm protein 30Kc6 dramatically improved the conditions of the atherosclerotic rabbits by decreasing serum levels of total triglyceride (TG, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C and total cholesterol (TC. Furthermore, 30Kc6 alleviated the extent of lesions in aorta and liver in the atherosclerotic rabbits. These data are not only helpful in understanding the anti

  3. Treatment patterns and low-density lipoprotein cholesterol (LDL-C) goal attainment among patients receiving high- or moderate-intensity statins.

    Science.gov (United States)

    Fox, Kathleen M; Tai, Ming-Hui; Kostev, Karel; Hatz, Maximilian; Qian, Yi; Laufs, Ulrich

    2018-05-01

    European clinical guidelines recommend a low-density lipoprotein cholesterol (LDL-C) goal of C goal attainment among atherosclerotic CV disease (ASCVD) patients with various utilization patterns of moderate- or high-intensity statins in routine care. This retrospective cohort study used electronic medical records data from the QuintilesIMS® Disease Analyzer (> 2 million individuals annually) to identify ASCVD (coronary atherosclerosis, stable/unstable angina, myocardial infarction, ischemic stroke, transient ischemic attack, aneurysm, peripheral artery disease) patients on moderate-/high-intensity statin in Germany. Proportion of patients with LDL-C C value for each patient (index) in 2012, 2013, and 2014, while on statin. Treatment patterns were assessed for patients with at least 1 year of post-index follow-up. Results were stratified by year and treatment pattern [no change, switch, dose up-/down-titration, discontinuation (≥ 90 day gap)]. In > 14,000 patients assessed in each year (mean age 71 years, 35% female, 8-12% taking high-intensity statins), approximately 80% had LDL-C ≥ 70 mg/dL. Treatment patterns were assessed for most (88-93%) patients. Approximately 79-81% of patients made no change to statin regimens, 1% switched statins, 14-16% discontinued; 1% of moderate-intensity patients up-titrated, and 3% of all patients down-titrated. LDL-C goal attainment in these treatment pattern groups was 20, 16-24, 17, 11-14, and 17-19%, respectively. Majority of ASCVD patients had LDL-C ≥ 70 mg/dL while on moderate-/high-intensity statins. Despite low LDL-C goal attainment, few patients changed their treatment regimens.

  4. A lipoprotein lipase mutation (Asn291Ser) is associated with reduced HDL cholesterol levels in premature atherosclerosis

    NARCIS (Netherlands)

    Reymer, P.W.A.; Gagné, S E; Groenemeyer, B E; Zhang, H; Forsyth, I; Jansen, H; Seidell, J C; Kromhout, D.; Lie, K E; Kastelein, J.J.

    1995-01-01

    A reduction of high density lipoprotein cholesterol (HDC) is recognized as an important risk factor for coronary artery disease (CAD). We now show in approximately 1 in 20 males with proven atherosclerosis that an Asn291Ser mutation in the human lipoprotein lipase (LPL) gene is associated with

  5. Association between non-high-density lipoprotein cholesterol concentrations and mortality from coronary heart disease among Japanese men and women: the Ibaraki Prefectural Health Study.

    Science.gov (United States)

    Noda, Hiroyuki; Iso, Hiroyasu; Irie, Fujiko; Sairenchi, Toshimi; Ohtaka, Emiko; Ohta, Hitoshi

    2010-02-01

    The aim of this study was to examine whether non-high-density lipoprotein cholesterol (non-HDL-cholesterol) raises the risk of coronary heart disease in a dose-response fashion in a non-obese population with low total cholesterol levels and high HDL-cholesterol levels, such as Japanese. A total of 30,802 men and 60,417 women, aged 40 to 79 years with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance through 2003 identified 539 coronary heart disease deaths. The mean values for non-HDL-cholesterol were 140 mg/dL for men and 151 mg/dL for women. The corresponding mean values were 193 mg/dL and 208 mg/dL total cholesterol and 52 mg/dL and 57 mg/dL HDL-cholesterol, respectively. Men with non-HDL-cholesterol > or = 180 mg/dL had a two-fold higher age-adjusted risk of mortality from coronary heart disease than did those with non-HDL-cholesterol or = 180 mg/dL versus <100 mg/dL of non-HDL-cholesterol was 2.22 (95% confidence interval: 1.37 to 3.62) for men and 0.71 (0.37 to 1.34) for women. Higher concentrations of non-HDL-cholesterol were associated with an increased risk of mortality from coronary heart disease for men, but not for women.

  6. Accumulation of low density lipoprotein associated cholesterol in calcifying vesicle fractions correlates with intimal thickening in thoracic aortas of juvenile rabbits fed a supplemental cholesterol diet

    Directory of Open Access Journals (Sweden)

    Culley Nathan C

    2006-10-01

    Full Text Available Abstract Background It has been shown that calcifying vesicles play an important role in aortic calcification and that cholesterol content in the isolated vesicle fraction is increased when rabbits are fed supplemental cholesterol diets. Whether lipoprotein-associated cholesterols and other lipids are also increased in the vesicle fraction and whether the increase correlates with atherosclerosis remain unknown. Results Fourteen juvenile male rabbits fed an atherogenic diet containing 0.5% cholesterol and 2% peanut oil for 3 months developed varying degrees of hypercholesterolemia and intimal thickening in the ascending thoracic aorta. The correlation between these two parameters was insignificant, and likely attributable to the use of small numbers of rabbits in this study. Despite this lack of correlation, we demonstrate that the accumulation of cholesterol in calcifying vesicle fractions obtained from the collagenase-digested aorta fragments correlates well with intimal thickening (r2 = 0.98, p Conclusion When limited numbers of rabbits are used, LDL-C accumulation in calcifying vesicle fractions is a better biomarker for atherosclerosis than LDL-C levels in the serum. The close association of LDL-C with calcifying vesicles may play an important role in atherosclerosis and calcification.

  7. Low-density lipoproteins cause atherosclerotic cardiovascular disease

    DEFF Research Database (Denmark)

    Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian

    2017-01-01

    Aims To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). Methods and results We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from...... proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects. Conclusion Consistent evidence from...

  8. Significance of oxidized low-density lipoprotein in body fluids as a marker related to diseased conditions.

    Science.gov (United States)

    Itabe, Hiroyuki; Kato, Rina; Sasabe, Naoko; Obama, Takashi; Yamamoto, Matsuo

    2018-03-06

    Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of oxLDL and LDL rather than oxLDL concentration alone has been focused attention. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in circulatory system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  9. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase.

    Science.gov (United States)

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M; Brown, Robert J

    2014-09-05

    Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    NARCIS (Netherlands)

    D. Postmus (Douwe); H. Warren (Helen); S. Trompet (Stella); B.J. Arsenault (Benoit J.); C.L. Avery; J.C. Bis (Joshua); D.I. Chasman (Daniel); C.E. de Keyser (Catherina Elisabeth); H. Deshmukh (Harshal); D.S. Evans (Daniel); Feng, Q. (QiPing); X. Li (Xiaohui); Smit, R.A.J. (Roelof A.J.); A.V. Smith (Albert Vernon); F. Sun (Fangui); K.D. Taylor (Kent); A.M. Arnold (Alice M.); M.J. Barnes (Michael); B.J. Barratt (Bryan J.); J. Betteridge (John); S.M. Boekholdt (Matthijs); E.A. Boerwinkle (Eric); B.M. Buckley (Brendan M.); Y.D. Chen (Y.); A.J. de Craen (Anton); S. Cummings; Denny, J.C. (Joshua C.); G.P. Dubé (Gregory); P.N. Durrington (Paul); G. Eiriksdottir (Gudny); I. Ford (Ian); X. Guo (Xiuqing); T.B. Harris (Tamara); S.R. Heckbert (Susan); A. Hofman (Albert); G. Kees Hovingh; J.J.P. Kastelein (John); Launer, L.J. (Leonore J.); Liu, C.-T. (Ching-Ti); Y. Liu (YongMei); T. Lumley (Thomas); P.M. Mckeigue (Paul); P. Munroe (Patricia); A. Neil (Andrew); D.A. Nickerson (Deborah); F. Nyberg (Fredrik); E. O'Brien (Eoin); C.J. O'Donnell (Christopher); W.S. Post (Wendy S.); N.R. Poulter (Neil); R.S. Vasan (Ramachandran Srini); K.M. Rice (Kenneth); S.S. Rich (Stephen); F. Rivadeneira Ramirez (Fernando); N. Sattar (Naveed); P. Sever (Peter); S. Shaw-Hawkins (Sue); D.C. Shields (Denis C.); P.E. Slagboom (Eline); N.L. Smith (Nicholas); J.D. Smith (Joshua D.); N. Sotoodehnia (Nona); A. Stanton (Alice); D.J. Stott (David. J.); B.H.Ch. Stricker (Bruno); T. Stürmer; A.G. Uitterlinden (André); W.-Q. Wei (Wei-Qi); R.G.J. Westendorp (Rudi); E.A. Whitsel (Eric A.); K.L. Wiggins (Kerri); R.A. Wilke (Russell A.); C. Ballantyne (Christie); H.M. Colhoun (H.); L.A. Cupples (Adrienne); O.H. Franco (Oscar); V. Gudnason (Vilmundur); G.A. Hitman (Graham); C.N.A. Palmer (Colin); B.M. Psaty (Bruce); P.M. Ridker (Paul); J.M. Stafford (Jeanette M.); Stein, C.M. (Charles M.); J.-C. Tardif (Jean-Claude); M. Caulfield (Mark); J.W. Jukema (Jan Wouter); Rotter, J.I. (Jerome I.); R.M. Krauss (Ronald)

    2016-01-01

    textabstractBackground In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We

  11. Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

    Science.gov (United States)

    Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

    1986-02-12

    Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

  12. Low density lipoprotein: structure, dynamics, and interactions of apoB-100 with lipids

    DEFF Research Database (Denmark)

    Murtola, T.; Vuorela, T. A.; Hyvonen, M. T.

    2011-01-01

    's structural information makes it more difficult to understand its function. In this work, we have combined experimental and theoretical data to construct LDL models comprised of the apoB-100 protein wrapped around a lipid droplet of about 20 nm in size. The models are considered by near-atomistic multi......-microsecond simulations to unravel structural as well as dynamical properties of LDL, with particular attention paid to lipids and their interactions with the protein. We find that the distribution and the ordering of the lipids in the LDL particle are rather complex. The previously proposed 2- and 3- layer models turn......Low-density lipoprotein (LDL) transports cholesterol in the bloodstream and plays an important role in the development of cardiovascular diseases, in particular atherosclerosis. Despite its importance to health, the structure of LDL is not known in detail. This is worrying since the lack of LDL...

  13. α-Tocopherol modulates the low density lipoprotein receptor of human HepG2 cells

    Directory of Open Access Journals (Sweden)

    Bottema Cynthia DK

    2003-05-01

    Full Text Available Abstract The aim of this study was to determine the effects of vitamin E (α-tocopherol on the low density lipoprotein (LDL receptor, a cell surface protein which plays an important role in controlling blood cholesterol. Human HepG2 hepatoma cells were incubated for 24 hours with increasing amounts of α, δ, or γ-tocopherol. The LDL receptor binding activity, protein and mRNA, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA reductase mRNA, cell cholesterol and cell lathosterol were measured. The effect of α-tocopherol was biphasic. Up to a concentration of 50 μM, α-tocopherol progressively increased LDL receptor binding activity, protein and mRNA to maximum levels 2, 4 and 6-fold higher than control, respectively. The HMG-CoA reductase mRNA and the cell lathosterol concentration, indices of cholesterol synthesis, were also increased by 40% over control by treatment with 50 μM α-tocopherol. The cell cholesterol concentration was decreased by 20% compared to control at 50 μM α-tocopherol. However, at α-tocopherol concentrations higher than 50 μM, the LDL receptor binding activity, protein and mRNA, the HMG-CoA reductase mRNA and the cell lathosterol and cholesterol concentrations all returned to control levels. The biphasic effect on the LDL receptor was specific for α-tocopherol in that δ and γ-tocopherol suppressed LDL receptor binding activity, protein and mRNA at all concentrations tested despite the cells incorporating similar amounts of the three homologues. In conclusion, α-tocopherol, exhibits a specific, concentration-dependent and biphasic "up then down" effect on the LDL receptor of HepG2 cells which appears to be at the level of gene transcription. Cholesterol synthesis appears to be similarly affected and the cell cholesterol concentration may mediate these effects.

  14. Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy.

    Science.gov (United States)

    Lebdai, Souhil; Mathieu, Romain; Leger, Julie; Haillot, Olivier; Vincendeau, Sébastien; Rioux-Leclercq, Nathalie; Fournier, Georges; Perrouin-Verbe, Marie-Aimée; Doucet, Laurent; Azzouzi, Abdel Rahmene; Rigaud, Jérome; Renaudin, Karine; Charles, Thomas; Bruyere, Franck; Fromont, Gaelle

    2018-02-01

    Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP). All patients consecutively treated for PCa by RP in 6 academic institutions between August 2013 and July 2016 were included. MetS was defined as at least 3 of 5 components (obesity, elevated blood pressure, diabetes, low high-density lipoprotein (HDL)-cholesterol, and hypertriglyceridemia). Demographic, biological, and clinical parameters were prospectively collected, including: age, biopsy results, preoperative serum prostate-specific antigen, surgical procedure, and pathological data of RP specimen. Locally advanced disease was defined as a pT-stage ≥3. International Society of Urological Pathology (ISUP) groups were used for pathological grading. Qualitative and quantitative variables were compared using chi-square and Wilcoxon tests; logistic regression analyses assessed the association of MetS and its components with pathological data. Statistical significance was defined as a P<0.05. Among 567 men, 249 (44%) had MetS. In a multivariate model including preoperative prostate-specific antigen, biopsy ISUP-score, clinical T-stage, age, and ethnicity: we found that MetS was an independent risk factor for positive margins, and ISUP group ≥4 on the RP specimen (odds ratio [OR] = 1.5; 95% CI: 1.1-2.3; P = 0.035; OR = 2.0; 95% CI: 1.1-4.0; P = 0.044, respectively). In addition, low HDL-cholesterol level was associated with locally advanced PCa (OR = 1.6; 95% CI: 1.1-2.4; P = 0.024). Risks of adverse pathological features increased with the number of MetS components: having ≥ 4 MetS components was significantly associated with higher risk of ISUP group ≥ 4 and higher risk of positive margins (OR = 1.9; 95% CI: 1.1-3.3; P = 0.017; OR = 1.8; 95% CI: 1.1-2.8; P = 0.007, respectively). MetS was an independent predictive factor for

  15. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    NARCIS (Netherlands)

    Postmus, Iris; Warren, Helen R.; Trompet, Stella; Arsenault, Benoit J.; Avery, Christy L.; Bis, Joshua C.; Chasman, Daniel I.; de Keyser, Catherine E.; Deshmukh, Harshal A.; Evans, Daniel S.; Feng, QiPing; Li, Xiaohui; Smit, Roelof A. J.; Smith, Albert V.; Sun, Fangui; Taylor, Kent D.; Arnold, Alice M.; Barnes, Michael R.; Barratt, Bryan J.; Betteridge, John; Boekholdt, S. Matthijs; Boerwinkle, Eric; Buckley, Brendan M.; Chen, Y.-D. Ida; de Craen, Anton J. M.; Cummings, Steven R.; Denny, Joshua C.; Dubé, Marie Pierre; Durrington, Paul N.; Eiriksdottir, Gudny; Ford, Ian; Guo, Xiuqing; Harris, Tamara B.; Heckbert, Susan R.; Hofman, Albert; Hovingh, G. Kees; Kastelein, John J. P.; Launer, Leonore J.; Liu, Ching-Ti; Liu, Yongmei; Lumley, Thomas; McKeigue, Paul M.; Munroe, Patricia B.; Neil, Andrew; Nickerson, Deborah A.; Nyberg, Fredrik; O'Brien, Eoin; O'Donnell, Christopher J.; Post, Wendy; Poulter, Neil; Vasan, Ramachandran S.; Rice, Kenneth; Rich, Stephen S.; Rivadeneira, Fernando; Sattar, Naveed; Sever, Peter; Shaw-Hawkins, Sue; Shields, Denis C.; Slagboom, P. Eline; Smith, Nicholas L.; Smith, Joshua D.; Sotoodehnia, Nona; Stanton, Alice; Stott, David J.; Stricker, Bruno H.; Stürmer, Til; Uitterlinden, André G.; Wei, Wei-Qi; Westendorp, Rudi G. J.; Whitsel, Eric A.; Wiggins, Kerri L.; Wilke, Russell A.; Ballantyne, Christie M.; Colhoun, Helen M.; Cupples, L. Adrienne; Franco, Oscar H.; Gudnason, Vilmundur; Hitman, Graham; Palmer, Colin N. A.; Psaty, Bruce M.; Ridker, Paul M.; Stafford, Jeanette M.; Stein, Charles M.; Tardif, Jean-Claude; Caulfield, Mark J.; Jukema, J. Wouter; Rotter, Jerome I.; Krauss, Ronald M.

    2016-01-01

    In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. We performed a meta-analysis of genome-wide

  16. Changes in the serum profiles of lipids and cholesterol in sheep ...

    African Journals Online (AJOL)

    The samples were used for haematological and parasitological analyses and determination of serum concentrations of total cholesterol, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol) and low density lipoproteincholesterol (LDL-cholesterol). All animals in the infected group showed parasitaemia by day ...

  17. Serum cholesterol as a risk factor for coronary heart disease revisited

    African Journals Online (AJOL)

    2014-08-04

    Aug 4, 2014 ... levels to low-density lipoprotein (LDL) cholesterol levels, and high- density ... intestinal absorption of triglycerides and cholesterol, plus very low- ... These relationships are present across the age spectrum and in both sexes.

  18. Two novel mutations in exon 3 and 4 of low density lipoprotein (LDL) receptor gene in patients with heterozygous familial hypercholesterolemia

    International Nuclear Information System (INIS)

    Khan, S.P.

    2011-01-01

    Objective: To determine the common mutation of low density lipoprotein receptor in hypercholesterolemia patients requiring screening for heterozygous familial hypercholesterolemia (HeFH) in Karachi. Study Design: Case-series. Place and Duration of Study: Dr. Ziauddin Hospital Laboratory and Dr. Rubina Ghani's Pathological and Molecular Laboratories, Karachi, for the PCR bench work from June 2008 to October 2009. Methodology: All the patients selected for this study were from Dr. Ziauddin Hospital and National Institute of Cardiovascular Diseases. All the patients having high total cholesterol and LDL-cholesterol were included in this study with premature coronary artery diseases or a family history of hypercholesterolemia. Exclusion criteria included Diabetes mellitus, hypertension, renal disease, hypothyroidism and steroid therapy. After lipid profile with overnight fasting, DNA was extracted from whole blood collected in EDTA (ethylenediamine tetra acetic acid) tube and multiplex PCR (polymerase chain reaction) using forward and reverse primers of exons 3, 4, 9 and 14 of base pairs 162, 431, 550 and 496 respectively. Results: Out of total of 120 hypercholesterolemia cases, 42 patients were classical cases of HeFH (heterozygous familial hypercholesterolemia) with xanthomas, xanthelasmas and LDL-C > 160 mg/dl. The total cholesterol (260 +- 57 mg/dL) and LDL-C (192 +- 39 mg/dL ) of cases was significantly high as compared to, controls having total cholesterol (184 9 +- 27 mg/dL) and LDL-C (105 +- 22 mg/dL), p > 0.001. Two novel point mutations were noted in exon 3 and exon 4. The other 78 cases were probable with raised LDL-C (low density lipoprotein cholesterol) and family history of premature coronary heart diseases. Conclusion: The frequency of HeFH was 35% classical and 65% probable cases out of total 120 hypercholesterolemia patients from two tertiary care hospitals in Karachi. The point mutation on exon 3 and exon 4 of LDLR gene was the most common. PCR is

  19. Influence of low cholesterol eggs enriched with vitamin-E and omega-3 fatty acid on blood lipid profile of Wistar rats.

    Science.gov (United States)

    Taneja, S K; Rakha, Aruna

    2005-07-01

    In the recent past, low cholesterol eggs enriched with vitamin-E and omega-3 fatty acid have been developed and are marketed under different brands claiming them as heart friendly. The influence of these eggs (smart eggs) on lipid profile of rats was evaluated in comparison to that of the standard eggs. Data of 4 week dietary treatment revealed that total plasma cholesterol, low density lipoprotein (LDL) and very low density lipoprotein (VLDL) cholesterol increased only 22% in rats fed on diet containing 4 smart eggs per kg of semi-synthetic diet in contrast to the increase of more than 100 % when fed on diet containing standard eggs. The results suggest that it is not the low cholesterol content alone but also vitamin E and omega-3 fatty acids present in smart eggs that act synergically to prevent a substantial change in blood lipid profile and impose no serious risk to the health of the consumers.

  20. Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops).

    Science.gov (United States)

    Chauke, Chesa G; Arieff, Zainunisha; Kaur, Mandeep; Seier, Jurgen V

    2014-02-01

    Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.

  1. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  2. Peri and Postparturient Concentrations of Lipid Lipoprotein Insulin and Glucose in Normal Dairy Cows

    OpenAIRE

    BAŞOĞLU, Abdullah; SEVİNÇ, Mutlu; OK, Mahmut

    1998-01-01

    In order to provide uniqe insight into the metabolic disturbences seen after calving cholesterol, triglycerid, high density lipoprotein, low density lipoprotein, very low density lipoprotein, glucose and insulin levels in serum were studied before calving (group I), in aerly (group II) and late (group III) lactation in 24 normal cows. Serum lipoproteins were separeted into various density classes by repeated ultracentrifugation. The results indicate that there was a rise in glucose, trygl...

  3. Kaempferol stimulates gene expression of low-density lipoprotein receptor through activation of Sp1 in cultured hepatocytes

    Science.gov (United States)

    Ochiai, Ayasa; Miyata, Shingo; Iwase, Masamori; Shimizu, Makoto; Inoue, Jun; Sato, Ryuichiro

    2016-01-01

    A high level of plasma low-density lipoprotein (LDL) cholesterol is considered a risk factor for atherosclerosis. Because the hepatic LDL receptor (LDLR) is essential for clearing plasma LDL cholesterol, activation of LDLR is a promising therapeutic target for patients with atherosclerotic disease. Here we demonstrated how the flavonoid kaempferol stimulated the gene expression and activity of LDLR in HepG2 cells. The kaempferol-mediated stimulation of LDLR gene expression was completely inhibited by knockdown of Sp1 gene expression. Treatment of HepG2 cells with kaempferol stimulated the recruitment of Sp1 to the promoter region of the LDLR gene, as well as the phosphorylation of Sp1 on Thr-453 and Thr-739. Moreover, these kaempferol-mediated processes were inhibited in the presence of U0126, an ERK pathway inhibitor. These results suggest that kaempferol may increase the activity of Sp1 through stimulation of Sp1 phosphorylation by ERK1/2 and subsequent induction of LDLR expression and activity. PMID:27109240

  4. Effects of 1,2-cyclohexanedione modification on the metabolism of very low density lipoprotein apolipoprotein B: potential role of receptors in intermediate density lipoprotein catabolism

    International Nuclear Information System (INIS)

    Packard, C.J.; Boag, D.E.; Clegg, R.; Bedford, D.; Shepherd, J.

    1985-01-01

    The conversion of very low density (VLDL) to low density lipoproteins (LDL) is a two-step process. The first step is mediated by lipoprotein lipase, but the mechanism responsible for the second is obscure. In this study we examined the possible involvement of receptors at this stage. Apolipoprotein B (apoB)-containing lipoproteins were separated into three fractions, VLDL (Sf 100-400), an intermediate fraction IDL (Sf 12-100), and LDL (Sf 0-12). Autologous 125I-labeled VLDL and 131I-labeled 1,2-cyclohexanedione-modified VLDL were injected into the plasma of four normal subjects and the rate of transfer of apoB radioactivity was followed through IDL to LDL. Modification did not affect VLDL to IDL conversion. Thereafter, however, the catabolism of modified apoB in IDL was retarded and its appearance in LDL was delayed. Hence, functional arginine residues (and by implication, receptors) are required in this process. Confirmation of this was obtained by injecting 125I-labeled IDL and 131I-labeled cyclohexanedione-treated IDL into two additional subjects. Again, IDL metabolism was delayed by approximately 50% as a result of the modification. These data are consistent with the view that receptors are involved in the metabolism of intermediate density lipoprotein

  5. Nonpharmacological lipoprotein apheresis reduces arterial inflammation in familial hypercholesterolemia

    NARCIS (Netherlands)

    van Wijk, Diederik F.; Sjouke, Barbara; Figueroa, Amparo; Emami, Hamed; van der Valk, Fleur M.; MacNabb, Megan H.; Hemphill, Linda C.; Schulte, Dominik M.; Koopman, Marion G.; Lobatto, Mark E.; Verberne, Hein J.; Fayad, Zahi A.; Kastelein, John J. P.; Mulder, Willem J. M.; Hovingh, G. Kees; Tawakol, Ahmed; Stroes, Erik S. G.

    2014-01-01

    Patients with familial hypercholesterolemia (FH) are characterized by elevated atherogenic lipoprotein particles, predominantly low-density lipoprotein cholesterol (LDL-C), which is associated with accelerated atherogenesis and increased cardiovascular risk. This study used (18)F-fluorodeoxyglucose

  6. Unique Features of High-Density Lipoproteins in the Japanese: In Population and in Genetic Factors

    Directory of Open Access Journals (Sweden)

    Shinji Yokoyama

    2015-04-01

    Full Text Available Despite its gradual increase in the past several decades, the prevalence of atherosclerotic vascular disease is low in Japan. This is largely attributed to difference in lifestyle, especially food and dietary habits, and it may be reflected in certain clinical parameters. Plasma high-density lipoprotein (HDL levels, a strong counter risk for atherosclerosis, are indeed high among the Japanese. Accordingly, lower HDL seems to contribute more to the development of coronary heart disease (CHD than an increase in non-HDL lipoproteins at a population level in Japan. Interestingly, average HDL levels in Japan have increased further in the past two decades, and are markedly higher than in Western populations. The reasons and consequences for public health of this increase are still unknown. Simulation for the efficacy of raising HDL cholesterol predicts a decrease in CHD of 70% in Japan, greater than the extent by reducing low-density lipoprotein cholesterol predicted by simulation or achieved in a statin trial. On the other hand, a substantial portion of hyperalphalipoproteinemic population in Japan is accounted for by genetic deficiency of cholesteryl ester transfer protein (CETP, which is also commonly unique in East Asian populations. It is still controversial whether CETP mutations are antiatherogenic. Hepatic Schistosomiasis is proposed as a potential screening factor for historic accumulation of CETP deficiency in East Asia.

  7. Lipoprotein lipase gene variants: Association with acute myocardial ...

    African Journals Online (AJOL)

    Mahyar Bahrami

    2015-05-13

    May 13, 2015 ... ated with acute myocardial infarction but with triglyceride levels. У 2015 The ... C) and low levels of high-density lipoprotein cholesterol. (HDL-C) are .... relationship between LDL, HDL, cholesterol and TG levels with LPL ...

  8. Association between high-density lipoprotein cholesterol level and pulmonary function in healthy Korean adolescents: the JS high school study.

    Science.gov (United States)

    Park, Ji Hye; Mun, Seyeon; Choi, Dong Phil; Lee, Joo Young; Kim, Hyeon Chang

    2017-12-11

    Accumulating evidence suggests that high-density lipoprotein (HDL) cholesterol is associated with pulmonary function and pulmonary disorders. The aim of this study was to evaluate the association between HDL cholesterol and pulmonary function in healthy adolescents. This cross-sectional study was based on data collected for the JS High School study. The analysis included 644 adolescents (318 male and 326 female) aged 15-16 years old and free from asthma or chronic obstructive pulmonary disease. Fasting blood samples were collected for hematologic and biochemical assessment. Forced vital capacity volume (FVC) and forced expiratory volume in the 1 s (FEV1) were measured using dry-rolling-seal spirometry. The associations between HDL cholesterol and pulmonary function were analyzed using multiple linear regression models. Among male adolescents, an increase of 1.0 mg/dL in HDL cholesterol was associated with 10 mL decrease in FVC (p = 0.013) and FEV1 (p = 0.013) after adjusting for age, height, weight, alcohol drinking, smoking, physical activity, systolic blood pressure, total cholesterol, triglyceride, and monthly household income. Percent predicted values of FVC (p = 0.036) and FEV1 (p = 0.017) were also inversely associated with HDL cholesterol. However, among female adolescents, HDL cholesterol level was not significantly associated with absolute or percent predictive value of FVC and FEV1. Higher HDL cholesterol level may be associated with decreased pulmonary function among healthy male adolescents. The sex differences observed in the association between HDL cholesterol and pulmonary function need further investigation.

  9. [Alterations in the protein content and dysfunction of high-density lipoproteins from hyperhomocysteinemic mice].

    Science.gov (United States)

    Julve, Josep; Errico, Teresa Laura; Chen, Xiangyu; Santos, David; Freixa, Júlia; Porcel, Inmaculada; Cubero, Esther; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2013-01-01

    The aim of this study was to evaluate the proteic changes in high-density lipoproteins (HDL) induced by methionine-induced hyperhomocysteinemia in mice and its relationship with two of their main antiatherogenic properties. The oral administration of methionine resulted in an elevation (~8 times) in the plasma concentration of homocysteine. Hyperhomocysteinemia was inversely correlated with the plasma concentration of HDL cholesterol and its main protein component of HDL, apolipoprotein (apo) A-I, respectively. The cholesterol efflux in vivo from macrophages to HDL was decreased in hyperhomocysteinemic mice compared with the control mice. However, the reverse cholesterol transport from macrophages to feces remained unchanged. On the other hand, the ability of HDL from hyperhomocysteinemic mice to prevent the oxidative modification of low-density lipoproteins (LDL) was found decreased and associated with a concomitant reduction in the plasma activity of paraoxonase-1 (PON1) and the plasma concentration of apoA-I, and with a relative reduction in the apoA-IV content (~1.5 times) in the hyperhomocysteinemic HDL, respectively. The decrease in the ability of HDL from hyperhomocysteinemic mice to prevent LDL from oxidation was associated with a decrease in the apoA-I, PON1 and apoA-IV. Copyright © 2013 Elsevier España, S.L. and SEA. All rights reserved.

  10. Onset of lipoprotein-supported steroidogenesis in differentiating granulosa cells of rats: cellular events involved in mediating FSH-enhanced uptake of low-density lipoproteins

    International Nuclear Information System (INIS)

    Foster, J.D.

    1987-01-01

    Luteal cells use lipoproteins as the main source of cholesterol in steroidogenesis. However, little is known about the mechanisms underlying hormonal control of lipoprotein uptake. Thus, the authors tested the hypothesis that FSH and androgens regulate low density lipoprotein (LDL)-supported steroidogenesis in maturing granulosa cells by affecting receptor-mediated endocytosis of LDL at a cellular level. For this, immature ovarian granulosa cells were cultured with or without hormones, compactin (de novo synthesis inhibitor), or unlabeled or labeled ( 125 I or gold particles) LDL. Nonhormone-treated cultures produced little progestin; FSH and FSH/androstenedione stimulated steroid secretion. Progestin production by hormone-, but not nonhormone-, treated cultures was decreased by compactin, suggesting that de novo synthesis provided sterol for steroidogenesis. EM quantitation of cells exposed to gold-LDL at 37 0 C revealed that, compared to nonhormone-treated cells, FSH-treated cells (1) bound and internalized more gold-LDL, (2) had a smaller percentage of gold-LDL at their surfaces, (3) displayed a faster apparent rate of LDL internalization and delivery to lysosomes, and (4) contained more gold-labeled lysosomes. Data from biochemical studies in which 125 I-LDL was used supported the morphological findings. In conclusion, this study demonstrates that FSH has important effects at the cellular level on LDL uptake, which seem to underlie the striking increase in progestin production accompanying granulosa cell differentiation

  11. Increased LDL cholesterol and CRP in infants of mothers with type 1 diabetes

    DEFF Research Database (Denmark)

    Lindegaard, Marie Louise Skakkebæk; Svarrer, Eva Martha Madsen; Damm, Peter

    2008-01-01

    Proatherogenic stimuli during foetal life may predispose to development of atherosclerosis in adulthood. Elevated plasma low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) expression is associated with increased risk of atherosclerosis.......Proatherogenic stimuli during foetal life may predispose to development of atherosclerosis in adulthood. Elevated plasma low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) expression is associated with increased risk of atherosclerosis....

  12. Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops)

    KAUST Repository

    Chauke, Chesa G.

    2014-01-22

    Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African green monkeys for 3 months. In the treated monkeys, low-density lipoprotein cholesterol concentrations decreased by 43% from baseline, whereas concentrations of HDL cholesterol and apolipoprotein A-I increased by 49% and 34%, respectively. The results suggest that in this primate model, a low dose of niacin can effectively increase concentrations of HDL cholesterol.©2014 Nature America, Inc. All rights reserved.

  13. Low-density lipoprotein apheresis in a pediatric patient of familial hypercholesterolemia: Primi experientia from a tertiary care center in North India

    Directory of Open Access Journals (Sweden)

    Kanchan Dogra

    2017-01-01

    Full Text Available Familial hypercholesterolemia (FH is an autosomal dominant disorder due to mutation of apolipoprotein-B receptor gene causing severe dyslipidemia. Lifestyle modification and medical treatment attenuate the disease progression, but as these fail to control the blood cholesterol levels, low-density lipoprotein (LDL apheresis comes forth as a treatment option. To the best of our knowledge, the following is the very first case of pediatric FH being treated by LDL-apheresis to be reported from India. A severely malnourished female child presented with yellowish skin lesions over different parts of the body, viz., bilateral Achilles tendon, both knees, elbows, both pinnae, and outer canthus of both eyes. She had a strong family history of borderline hypercholesterolemia and was diagnosed as a case of FH. She was maintained on diet modification. LDL-apheresis was planned as the cholesterol levels were not controlled with the diet modificationt. However, unavailability of an appropriate kit in India for LDL-apheresis led to the use of the modified PL1 kit meant for therapeutic plasma exchange procedures. We conducted two sessions of LDL-apheresis. After the first session, the LDL-cholesterol (LDL-C level fell by 75.9% and the total cholesterol fell by 73.5%. A second procedure led to a decline in total cholesterol level by 18.6% and LDL-C by 19.46%. Subsequently, she was advised diet modification and statin therapy with regular follow-up after every 6 months. Thus, the cascade filtration technique is a safe and effective treatment option for removing the undesired lipoproteins.

  14. High density lipoprotein cholesterol (HDL) metabolism and its role in ischemic heart disease

    International Nuclear Information System (INIS)

    Pirzado, Z.A.; Sngi, S.A.; Malik, R.

    1999-01-01

    Case control and prospective epidemiological studies have found a striking, consistently negative association between High Density Lipoprotein(HDL) levels and coronary vascular events. As a results, the genetic and environmental determinants of HDL levels are being studied intensively. These investigations and their potential clinical applications require a fundamental understanding of the structure, function and metabolism of HDL and its components. Of the special interest are the means by which it exerts its apparently protective effect. In this report we characterize the structure of HLD: and describe its compounds, particularly the protein component. We discuss HDL metabolism in light of the relationship of HDL to other lipoprotein classes and relate what little is known of the functions of HDL. We also review the biochemical mechanism by which HDL may protect against cardiovascular disease and discuss further biochemical research that will be necessary for a better understanding of HDL. Interest in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related in HDL has been greatly intensified in recent years, stimulated largely by the finding that HDL is inversely related to coronary artery disease. Case-control and prospective observations of the striking, consistent and independent negative association between HDL levels and coronary vascular events have in turn generated new interest in the structure, composition and metabolism of these fascinating lipoproteins. Several studies carried out in Pakistan also reveal the inverse relation of HDL to IHD/sup 1,2/. This article contains a tremendous amount of information on HDL and its relationship to genetic and environmental factors which should be useful to investigations and clinicians in their evaluation and use of HDL cholesterol measurements to assess hearth disease risk. A knowledge of the structure, function and metabolism of HDL and its components is

  15. The effect of insulin deficiency on the plasma clearance and exchange of high-density-lipoprotein phosphatidylcholine in rats.

    Science.gov (United States)

    Martins, I J; Redgrave, T G

    1992-01-01

    Triolein/cholesteryl oleate/cholesterol/phosphatidylcholine emulsions designed to model the lipid composition of chylomicrons were injected intravenously into control and streptozotocin-treated insulin-deficient rats. As previously described for lymph chylomicrons, the emulsion triolein was hydrolysed and phosphatidylcholine was transferred to the plasma high-density lipoproteins (HDL). This mechanism was used to introduce a phospholipid label into HDL in vivo. The subsequent clearance of phospholipid radioactivity from the plasma of insulin-deficient rats was significantly slower than in controls (P less than 0.025). Plasma clearance was similarly slower in insulin-deficient rats after injection of HDL that was previously labelled with radioactive phospholipids. After injection, the phospholipid label redistributed rapidly between the large-particle fraction of plasma lipoproteins (very-low- and low-density lipoproteins), and the lighter and heavier fractions of HDL. Compared with control rats, in insulin-deficient rats less of the phospholipid label was distributed to the lighter HDL fraction and more to the heavier HDL fraction, and this difference was not due to changes in activity of lecithin: cholesterol acyltransferase or in the apparent activity of phospholipid transfer protein. In insulin-deficient rats the changes in HDL phospholipid clearance and exchange appeared to be secondary to the associated hypertriglyceridaemia and the related changes in distribution of phospholipids between classes of plasma lipoproteins. PMID:1536661

  16. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of insulin resistance but not of β cell function in a Chinese population with different glucose tolerance status.

    Science.gov (United States)

    Zhou, Meicen; Zhu, Lixin; Cui, Xiangli; Feng, Linbo; Zhao, Xuefeng; He, Shuli; Ping, Fan; Li, Wei; Li, Yuxiu

    2016-06-07

    Triglyceride/high-density lipoprotein-cholesterol (TG/HDL-C) ratio was a surrogate marker of IR; however, the relationship of TG/HDL-C with IR might vary by ethnicity. This study aims to investigate whether lipid ratios-TG/HDL-C, cholesterol/high-density lipoprotein-cholesterol (TC/HDL-C) ratio, low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol (LDL-C/HDL-C)) could be potential clinical markers of insulin resistance (IR) and β cell function and further to explore the optimal cut-offs in a Chinese population with different levels of glucose tolerance. Four hundred seventy-nine subjects without a history of diabetes underwent a 75 g 2 h Oral Glucose Tolerance Test (OGTT). New-onset diabetes (n = 101), pre-diabetes (n = 186), and normal glucose tolerance (n = 192) were screened. IR was defined by HOMA-IR > 2.69. Based on indices (HOMA-β, early-phase disposition index [DI30], (ΔIns30/ΔGlu30)/HOMA-IR and total-phase index [DI120]) that indicated different phases of insulin secretion, the subjects were divided into two groups, and the lower group was defined as having inadequate β cell compensation. Logistic regression models and accurate estimates of the areas under receiver operating characteristic curves (AUROC) were obtained. In all of the subjects, TG/HDL, TC/HDL-C, LDL-C/HDL-C, and TG were significantly associated with IR. The AUROCs of TG/HDL-C and TG were 0.71 (95 % CI: 0.66-0.75) and 0.71 (95 % CI: 0.65-0.75), respectively. The optimal cut-offs of TG/HDL-C and TG for IR diagnosis were 1.11 and 1.33 mmol/L, respectively. The AUROCs of TC/HDL-C and LDL-C/HDL-C were 0.66 and 0.65, respectively, but they were not acceptable for IR diagnosis. TG/HDL-C,LDL-C/HDL-C and TG were significantly associated with HOMA-β, but AUROCs were less than 0.50; therefore, the lipid ratios could not be predictors of basal β cell dysfunction. None of the lipid ratios was associated with early-phase insulin secretion. Only TG/HDL-C and

  17. Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

    Science.gov (United States)

    Rolla, Roberta; De Mauri, Andreana; Valsesia, Ambra; Vidali, Matteo; Chiarinotti, Doriana; Bellomo, Giorgio

    2015-12-01

    Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents. In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events. Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values. Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.

  18. Obesity and high-density lipoprotein cholesterol in black and white 9- and 10-year-old girls : The National Heart, Lung, and Blood Institute Growth and Health Study

    NARCIS (Netherlands)

    Morrison, JA; Sprecher, D; McMahon, RP; Schreiber, GB; Khoury, PR

    It has been hypothesized that the role of obesity in the pathogenesis of coronary heart disease (CHD) may be mediated in part through its inverse relationship with high-density lipoprotein cholesterol (HDL-C). Obesity is inversely correlated with HDL-C, and HDL-C has been shown to be protective

  19. Combined measurement of plasma cystatin C and low-density lipoprotein cholesterol: A valuable tool for evaluating progressive supranuclear palsy.

    Science.gov (United States)

    Weng, Ruihui; Wei, Xiaobo; Yu, Bin; Zhu, Shuzhen; Yang, Xiaohua; Xie, Fen; Zhang, Mahui; Jiang, Ying; Feng, Zhong-Ping; Sun, Hong-Shuo; Xia, Ying; Jin, Kunlin; Chan, Piu; Wang, Qing; Gao, Xiaoya

    2018-07-01

    Progressive supranuclear palsy (PSP) was previously thought as a cause of atypical Parkinsonism. Although Cystatin C (Cys C) and low-density cholesterol lipoprotein-C (LDL-C) are known to play critical roles in Parkinsonism, it is unknown whether they can be used as markers to distinguish PSP patients from healthy subjects and to determine disease severity. We conducted a cross-sectional study to determine plasma Cys C/HDL/LDL-C levels of 40 patients with PSP and 40 healthy age-matched controls. An extended battery of motor and neuropsychological tests, including the PSP-Rating Scale (PSPRS), the Non-Motor Symptoms Scale (NMSS), Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE), was used to evaluate the disease severity. Receiver operating characteristic (ROC) curves were adopted to assess the prognostic accuracy of Cys C/LDL-C levels in distinguishing PSP from healthy subjects. Patients with PSP exhibited significantly higher plasma levels of Cys C and lower LDL-C. The levels of plasma Cys C were positively and inversely correlated with the PSPRS/NMSS and MMSE scores, respectively. The LDL-C/HDL-C ratio was positively associated with PSPRS/NMSS and GDS scores. The ROC curve for the combination of Cys C and LDL-C yielded a better accuracy for distinguishing PSP from healthy subjects than the separate curves for each parameter. Plasma Cys C and LDL-C may be valuable screening tools for differentiating PSP from healthy subjects; while they could be useful for the PSP intensifies and severity evaluation. A better understanding of Cys C and LDL-C may yield insights into the pathogenesis of PSP. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Accumulation of native and methylated low density lipoproteins by healing rabbit arterial wall

    International Nuclear Information System (INIS)

    Fischman, A.J.; Lees, A.M.; Lees, R.S.; Barlai-Kovach, M.; Strauss, H.W.

    1987-01-01

    To determine whether healing arterial wall accumulation of low density lipoproteins (LDL) is mediated by the high affinity LDL receptor, normocholesterolemic rabbits were injected with 125 I-LDL, /sup 99m/Tc-LDL, or the reductively methylated analogs of these compounds ( 125 I-MeLDL, /sup 99m/Tc-MeLDL), 1 month after balloon catheter deendothelialization of the abdominal aorta. If the mechanism of accumulation requires interaction with the LDL receptor, reductively methylated lipoproteins which do not bind to the receptor should not accumulate in healing arterial wall. Twenty-four hours after injection of labelled lipoproteins, each animal was injected with Evans blue dye, in order to distinguish reendothelialized from deendothelialized aorta. One hour after dye injection, the aorta was fixed, removed, divided into abdominal (ballooned) and thoracic (unballooned) regions and counted. For all lipoprotein preparations, there were three to four times as many counts in the abdominal as in the thoracic aorta. En face autoradiographs were made of the aortas that had been exposed to 125 I-labelled lipoproteins. In the autoradiographs, the areas of the lowest activity corresponded to the centers of healing endothelial islands. The most intense radioactivity for both lipoproteins occurred in the region of the leading edge of the endothelial islands where active endothelial regeneration was in progress. The overall distribution of native and MeLDL accumulation was the same. The results suggest that low density lipoproteins are accumulated in areas of active endothelial regeneration by a mechanism that does not involve the high affinity LDL receptor

  1. The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses

    NARCIS (Netherlands)

    Jacobs, D.M.; Mihaleva, V.V.; Schalkwijk, D.B. van; Graaf, A.A. de; Vervoort, J.; Dorsten, F.A. van; Ras, R.T.; Demonty, I.; Trautwein, E.A.; Duynhoven, J. van

    2015-01-01

    Scope: Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects

  2. Concentration, composition and apolipoprotein B species of very low density lipoprotein subfractions from normolipidemic and hypertriglyceridemic humans.

    Science.gov (United States)

    Bittolo Bon, G; Cazzolato, G; Zago, S; Avogaro, P

    1985-01-01

    Lipoproteins in the d less than 1.006 g/ml density range obtained form 13 healthy normolipidemic subjects and from 15 patients affected by primary endogenous hypertriglyceridemia after 14-h fasting were subfractionated by filtration in Biogel A-15 M columns. The mass values and chemical composition of very low density lipoprotein (VLDL) subfractions 1 and 2 thus obtained were studied. In each subfraction the behavior of apolipoprotein B (Apo B) was tested by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. VLDL2 was higher and richer in cholesterol and proteins than VLDL1, while the percentage content of triglycerides was lower. In hypertriglyceridemic patients both VLDL1 and VLDL2 were higher than in normolipidemic subjects, the difference being particularly evident for VLDL1. In both VLDL1 and VLDL2 of nearly all the subjects studied the presence in electrophoretic gels of a large Apo B-100 band and of a minor Apo B-48 band with the appropriate mobility of lymph chylomicrons was detected. The Apo B-100/Apo B-48 ratio was about 6 in VLDL1 and 24 in VLDL2. A trend of a reduced Apo B-100/Apo B-48 ratio was observed in VLDL1 of hypertriglyceridemic patients.

  3. Low-density-lipoprotein cholesterol concentrations and risk of incident diabetes

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Lyass, Asya; Larson, Martin G

    2015-01-01

    AIMS/HYPOTHESIS: Statins and niacin (nicotinic acid) reduce circulating LDL-cholesterol (LDL-C) levels by different mechanisms. Yet, both increase the risk of diabetes mellitus. Our objective was to relate blood LDL-C concentrations and a genetic risk score (GRS) for LDL-C to the risk of incident...

  4. Atherosclerosis in low density lipoprotein receptor knockout mice fed cholesterol and soybean oil

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Olsen, P.; Frandsen, H.

    1999-01-01

    In order to study aortic atherosclerosis and atherosclerotic response to dietary cholesterol and soybean oil in homozygous LDLR-/- mice, the 16 weeks old animals were randomized in 4 groups either fed standard diet (no cholesterol added, group I, 12 male and 12 female), standard diet added 0.......5% cholesterol (group II, 12 male and 12 female), standard diet added 10% soybean oil (group Iii, 7 male) or standard diet added 0.5% cholesterol and 10% soybean oil (group IV, 7 male) for 14 weeks. At termination, the plasma cholesterol of males was: 9.4 mmol/I +/- 0.3 (SD) (group I), 34.4 +/- 6.2 (group II), 9...

  5. Aggregation and fusion of low-density lipoproteins in vivo and in vitro

    Science.gov (United States)

    Gursky, Olga

    2014-01-01

    Low-density lipoproteins (LDLs, also known as ‘bad cholesterol’) are the major carriers of circulating cholesterol and the main causative risk factor of atherosclerosis. Plasma LDLs are 20- to 25-nm nanoparticles containing a core of cholesterol esters surrounded by a phospholipid monolayer and a single copy of apolipoprotein B (550 kDa). An early sign of atherosclerosis is the accumulation of LDL-derived lipid droplets in the arterial wall. According to the widely accepted ‘response-to-retention hypothesis’, LDL binding to the extracellular matrix proteoglycans in the arterial intima induces hydrolytic and oxidative modifications that promote LDL aggregation and fusion. This enhances LDL uptake by the arterial macrophages and triggers a cascade of pathogenic responses that culminate in the development of atherosclerotic lesions. Hence, LDL aggregation, fusion, and lipid droplet formation are important early steps in atherogenesis. In vitro, a variety of enzymatic and nonenzymatic modifications of LDL can induce these reactions and thereby provide useful models for their detailed analysis. Here, we summarize current knowledge of the in vivo and in vitro modifications of LDLs leading to their aggregation, fusion, and lipid droplet formation; outline the techniques used to study these reactions; and propose a molecular mechanism that underlies these pro-atherogenic processes. Such knowledge is essential in identifying endogenous and exogenous factors that can promote or prevent LDL aggregation and fusion in vivo and to help establish new potential therapeutic targets to decelerate or even block these pathogenic reactions. PMID:25197325

  6. Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

    International Nuclear Information System (INIS)

    Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

    2004-01-01

    Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

  7. Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis.

    Science.gov (United States)

    Ephraim, Richard K D; Adu, Patrick; Ake, Edem; Agbodzakey, Hope; Adoba, Prince; Cudjoe, Obed; Agoni, Clement

    2016-01-01

    Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8-28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8-38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) ( p = 0.001) and high-density lipoprotein cholesterol (HDL-C) ( p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6-0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05-2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

  8. Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression

    DEFF Research Database (Denmark)

    Xu, Cang-Bao; Zheng, Jian-Pu; Zhang, Wei

    2014-01-01

    Vasoconstrictive endothelin type B (ET(B)) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ET(B) receptor expression and if extracellular signal...

  9. Cholesterol delivery to the adrenal glands estimated by adrenal venous sampling: An in vivo model to determine the contribution of circulating lipoproteins to steroidogenesis in humans.

    Science.gov (United States)

    Buitenwerf, Edward; Dullaart, Robin P F; Muller Kobold, Anneke C; Links, Thera P; Sluiter, Wim J; Connelly, Margery A; Kerstens, Michiel N

    Cholesterol, required for adrenal steroid hormone synthesis, is at least in part derived from circulating lipoproteins. The contribution of high-density lipoproteins (HDL) and low-density lipoproteins (LDL) to adrenal steroidogenesis in humans is unclear. The aim of the study was to determine the extent to which HDL and LDL are taken up by the adrenal glands using samples obtained during adrenal venous sampling (AVS). AVS was successfully performed in 23 patients with primary aldosteronism. Samples were drawn from both adrenal veins and inferior vena cava (IVC). HDL cholesterol (HDL-C) and lipoprotein particle profiles were determined by nuclear magnetic resonance spectroscopy. Apolipoprotein (apo) A-I and apoB were assayed by immunoturbidimetry. Plasma HDL-C and HDL and LDL particle concentrations (HDL-P and LDL-P) were not lower in samples obtained from the adrenal veins compared with the IVC (HDL-C, P = .59; HDL-P, P = .06; LDL-P, P = .93). ApoB was lower in adrenal venous plasma than in IVC (P = .026; P lipoproteins and steroidogenesis. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  10. Endogenous Cholesterol Excretion Is Negatively Associated With Carotid Intima-Media Thickness in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Dávila-Román, Victor G; Ostlund, Richard E

    2017-12-01

    Epidemiological studies strongly suggest that lipid factors independent of low-density lipoprotein cholesterol contribute significantly to cardiovascular disease risk. Because circulating lipoproteins comprise only a small fraction of total body cholesterol, the mobilization and excretion of cholesterol from plasma and tissue pools may be an important determinant of cardiovascular disease risk. Our hypothesis is that fecal excretion of endogenous cholesterol is protective against atherosclerosis. Cholesterol metabolism and carotid intima-media thickness were quantitated in 86 nondiabetic adults. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 solubilized in a lipid emulsion and dietary cholesterol by cholesterol-d 5 and the nonabsorbable stool marker sitostanol-d 4 . Plasma and stool samples were collected while subjects consumed a cholesterol- and phytosterol-controlled metabolic kitchen diet and were analyzed by mass spectrometry. Carotid intima-media thickness was negatively correlated with fecal excretion of endogenous cholesterol ( r =-0.426; P cholesterol ( r =-0.472; P ≤0.0001), and daily percent excretion of cholesterol from the rapidly mixing cholesterol pool ( r =-0.343; P =0.0012) and was positively correlated with percent cholesterol absorption ( r =+0.279; P =0.0092). In a linear regression model controlling for age, sex, systolic blood pressure, hemoglobin A1c, low-density lipoprotein, high-density lipoprotein cholesterol, and statin drug use, fecal excretion of endogenous cholesterol remained significant ( P =0.0008). Excretion of endogenous cholesterol is strongly, independently, and negatively associated with carotid intima-media thickness. The reverse cholesterol transport pathway comprising the intestine and the rapidly mixing plasma, and tissue cholesterol pool could be an unrecognized determinant of cardiovascular disease risk not reflected in circulating lipoproteins. Further work is needed to relate measures of

  11. Oxidized low-density lipoprotein in children with familial hypercholesterolemia and unaffected siblings: effect of pravastatin

    NARCIS (Netherlands)

    Rodenburg, Jessica; Vissers, Maud N.; Wiegman, Albert; Miller, Elizabeth R.; Ridker, Paul M.; Witztum, Joseph L.; Kastelein, John J. P.; Tsimikas, Sotirios

    2006-01-01

    OBJECTIVES: To assess the role of oxidized phospholipids (OxPLs) in children with familial hypercholesterolemia (FH) and the effect of pravastatin. BACKGROUND: Oxidized phospholipids are a major component of oxidized low-density lipoprotein (OxLDL) and are bound to lipoprotein (a) [Lp(a)]. The

  12. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Michael D. Shapiro

    2017-02-01

    Full Text Available Cholesterol-rich, apolipoprotein B (apoB-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed.

  13. Low density lipoprotein subclasses and response to a low-fat diet in healthy men

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.; Dreon, D.M. [Lawrence Berkeley Lab., CA (United States). Life Sciences Div.

    1994-11-01

    Lipid and lipoprotein response to reduced dietary fat intake was investigated in relation to differences in distribution of LDL subclasses among 105 healthy men consuming high-fat (46%) and low-fat (24%) diets in random order for six weeks each. On high-fat, 87 subjects had predominantly large, buoyant LDL as measured by gradient gel electrophoresis and confirmed by analytic ultracentrifugation (pattern A), while the remainder had primarily smaller, denser LDL (pattern B). On low-fat, 36 men changed from pattern A to B. Compared with the 51 men in the stable A group, men in the stable B group (n = 18) had a three-fold greater reduction in LDL cholesterol and significantly greater reductions in plasma apoB and mass of intermediate (LDL II) and small (LDL III) LDL subtractions measured by analytic ultracentrifugation. In both stable A and change groups, reductions in LDL-cholesterol were not accompanied by reduced plasma apoB, consistent with the observation of a shift in LDL particle mass from larger, lipid-enriched (LDL I and II) to smaller, lipid-depleted (LDL III and IV) subfractions, without significant change in particle number. Genetic and environmental factors influencing LDL subclass distributions thus may also contribute substantially to interindividual variation in response to a low-fat diet.

  14. Lipoprotein receptors in cultured bovine endothelial cells

    International Nuclear Information System (INIS)

    Struempfer, A.E.M.

    1983-07-01

    In this study, receptors that may be involved in the uptake of low density lipoproteins (LDL) and low density lipoproteins which have been modified by acetylation (AcLDL), were characterized. Aortic epithelial cells were used and a cell culture system which closely resembled the in vivo monolayer was established. Endothelial cell and lipoprotein interactions were examined by incubating the cells with 125 l-labelled lipoproteins under various conditions. The receptor affinity of bovine aortic endothelial cells was higher for AcLDL than that for LDL. Competition studies demonstrated that there were two distinct receptors for LDL and AcLDL on the endothelial cells. AcLDL did not compete with LDL for the LDL receptor, and conversely LDL did not compete with AcLDL for the AcLDL receptor. The receptor activities for LDL and AcLDL were examined as a function of culture age. Whereas the LDL receptor could be regulated, the AcLDL receptor was not as susceptible to regulation. Upon exposing endothelial cells for 72 h to either LDL or AcLDL, it was found that the total amount of cellular cholesterol increased by about 50%. However, the increase of total cholesterol was largely in the form of free cholesterol. This is in contrast to macrophages, where the increase in total cholesterol upon exposure to AcLDL is largely in the form cholesteryl esters

  15. Immune Response to Lipoproteins in Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sonia Samson

    2012-01-01

    Full Text Available Atherosclerosis, the underlying cause of cardiovascular disease, is characterized by chronic inflammation and altered immune response. Cholesterol is a well-known risk factor associated with the development of cardiovascular diseases. Elevated serum cholesterol is unique because it can lead to development of atherosclerosis in animals and humans even in the absence of other risk factors. Modifications of low-density lipoproteins mediated by oxidation, enzymatic degradation, and aggregation result in changes in their function and activate both innate and adaptive immune system. Oxidized low-density lipoprotein (LDL has been identified as one of the most important autoantigens in atherosclerosis. This escape from self-tolerance is dependent on the formation of oxidized phospholipids. The emerging understanding of the importance of immune responses against oxidized LDL in atherosclerosis has focused attention on the possibility of development of novel therapy for atherosclerosis. This review provides an overview of immune response to lipoproteins and the fascinating possibility of developing an immunomodulatory therapy for atherosclerosis.

  16. TRIIODOTHYRONINE RAPIDLY LOWERS PLASMA-LIPOPROTEIN (A) IN HYPOTHYROID SUBJECTS

    NARCIS (Netherlands)

    DULLAART, RPF; VANDOORMAAL, JJ; HOOGENBERG, K; SLUITER, WJ

    Background: Increases in plasma low-density-lipoprotein (LDL) cholesterol and apolipoprotein B (apo-B) are well known in primary hypothyroidism, but it is uncertain whether thyroid dysfunction is associated with elevated levels of the atherogenic lipoprotein (a) (Lp(a)). Methods: The effect of

  17. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Toth PP

    2016-05-01

    Full Text Available Peter P Toth1,2 1Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, 2Preventive Cardiology, CGH Medical Center, Sterling, IL, USA Abstract: Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]. Elevated TG levels are associated with increased cardiovascular disease (CVD risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L] is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant's effect on TG levels correlating with the magnitude of the variant's effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by

  18. Domains of apolipoprotein E contributing to triglyceride and cholesterol homeostasis in vivo. Carboxyl-terminal region 203-299 promotes hepatic very low density lipoprotein-triglyceride secretion

    NARCIS (Netherlands)

    Kypreos, K.E.; Dijk, K.W. van; Zee, A. van der; Havekes, L.M.; Zannis, V.I.

    2001-01-01

    Apolipoprotein (apo) E has been implicated in cholesterol and triglyceride homeostasis in humans. At physiological concentration apoE promotes efficient clearance of apoE-containing lipoprotein remnants. However, high apoE plasma levels correlate with high plasma triglyceride levels. We have used

  19. Break the fast? Update on patient preparation for cholesterol testing.

    Science.gov (United States)

    Naugler, Christopher; Sidhu, Davinder

    2014-10-01

    To provide an update on the clinical usefulness of nonfasting versus fasting lipid testing to improve patient compliance, patient safety, and clinical assessment in cholesterol testing. Recommendations are identified as supported by good, fair, and poor (conflicting or insufficient) evidence, according to the classifications adopted by the Canadian Task Force on Preventive Health Care. Screening for dyslipidemia as a risk factor for coronary artery disease and management of lipid-lowering medications are key parts of primary care. Recent evidence has questioned the fasting requirement for lipid testing. In population-based studies, total cholesterol, high-density lipoprotein cholesterol, and non-low-density lipoprotein cholesterol all varied by an average of 2% with fasting status. For routine screening, nonfasting cholesterol measurement is now a reasonable alternative to a fasting cholesterol measurement. For patients with diabetes, the fasting requirement might be an important safety issue because of problems with hypoglycemia. For the monitoring of triglyceride and low-density lipoprotein cholesterol levels in patients taking lipid-lowering medications, fasting becomes more important. Fasting for routine lipid level determinations is largely unnecessary and unlikely to affect patient clinical risk stratification, while nonfasting measurement might improve patient compliance and safety. Copyright© the College of Family Physicians of Canada.

  20. Nanotechnology for Synthetic High Density Lipoproteins

    Science.gov (United States)

    Luthi, Andrea J.; Patel, Pinal C.; Ko, Caroline H.; Mutharasan, R. Kannan; Mirkin, Chad A.; Thaxton, C. Shad

    2014-01-01

    Atherosclerosis is the disease mechanism responsible for coronary heart disease (CHD), the leading cause of death worldwide. One strategy to combat atherosclerosis is to increase the amount of circulating high density lipoproteins (HDL), which transport cholesterol from peripheral tissues to the liver for excretion. The process, known as reverse cholesterol transport, is thought to be one of the main reasons for the significant inverse correlation observed between HDL blood levels and the development of CHD. This article highlights the most common strategies for treating atherosclerosis using HDL. We further detail potential treatment opportunities that utilize nanotechnology to increase the amount of HDL in circulation. The synthesis of biomimetic HDL nanostructures that replicate the chemical and physical properties of natural HDL provides novel materials for investigating the structure-function relationships of HDL and for potential new therapeutics to combat CHD. PMID:21087901

  1. Genetic spectrum of low density lipoprotein receptor gene variations in South Indian population.

    Science.gov (United States)

    ArulJothi, K N; Suruthi Abirami, B; Devi, Arikketh

    2018-03-01

    Low density lipoprotein receptor (LDLR) is a membrane bound receptor maintaining cholesterol homeostasis along with Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) and other genes of lipid metabolism. Any pathogenic variation in these genes alters the function of the receptor and leads to Familial Hypercholesterolemia (FH) and other cardiovascular diseases. This study was aimed at screening the LDLR, APOB and PCSK9 genes in Hypercholesterolemic patients to define the genetic spectrum of FH in Indian population. Familial Hypercholesterolemia patients (n=78) of South Indian Tamil population with LDL cholesterol and Total cholesterol levels above 4.9mmol/l and 7.5mmol/l with family history of Myocardial infarction were involved. DNA was isolated by organic extraction method from blood samples and LDLR, APOB and PCSK9 gene exons were amplified using primers that cover exon-intron boundaries. The amplicons were screened using High Resolution Melt (HRM) Analysis and the screened samples were sequenced after purification. This study reports 20 variations in South Indian population for the first time. In this set of variations 9 are novel variations which are reported for the first time, 11 were reported in other studies also. The in silico analysis for all the variations detected in this study were done to predict the probabilistic effect in pathogenicity of FH. This study adds 9 novel variations and 11 recurrent variations to the spectrum of LDLR gene mutations in Indian population. All these variations are reported for the first time in Indian population. This spectrum of variations was different from the variations of previous Indian reports. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Correlation of structural stability with functional remodeling of high-density lipoproteins: the importance of being disordered.

    Science.gov (United States)

    Guha, Madhumita; Gao, Xuan; Jayaraman, Shobini; Gursky, Olga

    2008-11-04

    High-density lipoproteins (HDLs) are protein-lipid assemblies that remove excess cell cholesterol and prevent atherosclerosis. HDLs are stabilized by kinetic barriers that decelerate protein dissociation and lipoprotein fusion. We propose that similar barriers modulate metabolic remodeling of plasma HDLs; hence, changes in particle composition that destabilize HDLs and accelerate their denaturation may accelerate their metabolic remodeling. To test this notion, we correlate existing reports on HDL-mediated cell cholesterol efflux and esterification, which are obligatory early steps in cholesterol removal, with our kinetic studies of HDL stability. The results support our hypothesis and show that factors accelerating cholesterol efflux and esterification in model discoidal lipoproteins (including reduced protein size, reduced fatty acyl chain length, and/or increased level of cis unsaturation) destabilize lipoproteins and accelerate their fusion and apolipoprotein dissociation. Oxidation studies of plasma spherical HDLs show a similar trend: mild oxidation by Cu(2+) or OCl(-) accelerates cell cholesterol efflux, protein dissociation, and HDL fusion, while extensive oxidation inhibits these reactions. Consequently, moderate destabilization may be beneficial for HDL functions by facilitating insertion of cholesterol and lipophilic enzymes, promoting dissociation of lipid-poor apolipoproteins, which are primary acceptors of cell cholesterol, and thereby accelerating HDL metabolism. Therefore, HDL stability must be delicately balanced to maintain the structural integrity of the lipoprotein assembly and ensure structural specificity necessary for interactions of HDL with its metabolic partners, while facilitating rapid HDL remodeling and turnover at key junctures of cholesterol transport. The inverse correlation between HDL stability and remodeling illustrates the functional importance of structural disorder in macromolecular assemblies stabilized by kinetic barriers.

  3. Improving lipoprotein profiles by liver-directed gene transfer of low ...

    Indian Academy of Sciences (India)

    cesses, where a myriad of proteins necessary for metabolism and immune .... containing 5% nonfat milk for several hours, the membrane .... high-density lipoprotein cholesterol; mice were fed with a high fat diet (21% fat, 0.15% choles- terol).

  4. HDL cholesterol response to GH replacement is associated with common cholesteryl ester transfer protein gene variation (-629C>A) and modified by glucocorticoid treatment

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; van den Berg, Gerrit; van der Knaap, Aafke M.; Dijck-Brouwer, Janneke; Dallinga-Thie, Geesje M.; Zelissen, Peter M. J.; Sluiter, Wim J.; van Beek, André P.

    2010-01-01

    GH replacement lowers total cholesterol and low-density lipoprotein cholesterol (LDL-C) in GH-deficient adults, but effects on high-density lipoprotein (HDL) cholesterol (HDL-C) are variable. Both GH and glucocorticoids decrease cholesteryl ester transfer protein (CETP) activity, which is important

  5. Agonistic Human Antibodies Binding to Lecithin-Cholesterol Acyltransferase Modulate High Density Lipoprotein Metabolism*

    Science.gov (United States)

    Gunawardane, Ruwanthi N.; Fordstrom, Preston; Piper, Derek E.; Masterman, Stephanie; Siu, Sophia; Liu, Dongming; Brown, Mike; Lu, Mei; Tang, Jie; Zhang, Richard; Cheng, Janet; Gates, Andrew; Meininger, David; Chan, Joyce; Carlson, Tim; Walker, Nigel; Schwarz, Margrit; Delaney, John; Zhou, Mingyue

    2016-01-01

    Drug discovery opportunities where loss-of-function alleles of a target gene link to a disease-relevant phenotype often require an agonism approach to up-regulate or re-establish the activity of the target gene. Antibody therapy is increasingly recognized as a favored drug modality due to multiple desirable pharmacological properties. However, agonistic antibodies that enhance the activities of the target enzymes are rarely developed because the discovery of agonistic antibodies remains elusive. Here we report an innovative scheme of discovery and characterization of human antibodies capable of binding to and agonizing a circulating enzyme lecithin cholesterol acyltransferase (LCAT). Utilizing a modified human LCAT protein with enhanced enzymatic activity as an immunogen, we generated fully human monoclonal antibodies using the XenoMouseTM platform. One of the resultant agonistic antibodies, 27C3, binds to and substantially enhances the activity of LCAT from humans and cynomolgus macaques. X-ray crystallographic analysis of the 2.45 Å LCAT-27C3 complex shows that 27C3 binding does not induce notable structural changes in LCAT. A single administration of 27C3 to cynomolgus monkeys led to a rapid increase of plasma LCAT enzymatic activity and a 35% increase of the high density lipoprotein cholesterol that was observed up to 32 days after 27C3 administration. Thus, this novel scheme of immunization in conjunction with high throughput screening may represent an effective strategy for discovering agonistic antibodies against other enzyme targets. 27C3 and other agonistic human anti-human LCAT monoclonal antibodies described herein hold potential for therapeutic development for the treatment of dyslipidemia and cardiovascular disease. PMID:26644477

  6. Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats.

    Science.gov (United States)

    Nammi, Srinivas; Kim, Moon S; Gavande, Navnath S; Li, George Q; Roufogalis, Basil D

    2010-05-01

    Zingiber officinale has been used to control lipid disorders and reported to possess remarkable cholesterol-lowering activity in experimental hyperlipidaemia. In the present study, the effect of a characterized and standardized extract of Zingiber officinale on the hepatic lipid levels as well as on the hepatic mRNA and protein expression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated in a high-fat diet-fed rat model. Rats were treated with an ethanol extract of Zingiber officinale (400 mg/kg) extract along with a high-fat diet for 6 weeks. The extract of Zingiber officinale significantly decreased hepatic triglyceride and tended to decrease hepatic cholesterol levels when administered over 6 weeks to the rats fed a high-fat diet. We found that in parallel, the extract up-regulated both LDL receptor mRNA and protein level and down-regulated HMG-CoA reductase protein expression in the liver of these rats. The metabolic control of body lipid homeostasis is in part due to enhanced cholesterol biosynthesis and reduced expression of LDL receptor sites following long-term consumption of high-fat diets. The present results show restoration of transcriptional and post-transcriptional changes in low-density lipoprotein and HMG CoA reductase by Zingiber officinale administration with a high-fat diet and provide a rational explanation for the effect of ginger in the treatment of hyperlipidaemia.

  7. Serum cholesterol as a risk factor for coronary heart disease revisited

    African Journals Online (AJOL)

    The biology of lipoproteins and lipoprotein particles as mediators of atherosclerosis has been documented extensively. Numerous prospective epidemiological studies have shown a robust relationship between low-density lipoprotein (LDL) cholesterol, or particles bearing apolipoprotein B, and increased risk of coronary ...

  8. Single Low-Density Lipoprotein Apheresis Does Not Improve Vascular Endothelial Function in Chronically Treated Hypercholesterolemic Patients

    Directory of Open Access Journals (Sweden)

    Kevin D. Ballard

    2016-01-01

    Full Text Available Objective. To investigate vascular endothelial function (VEF responses to a single low-density lipoprotein (LDL apheresis session in hypercholesterolemic patients undergoing chronic treatment. Methods. We measured brachial artery flow-mediated dilation (FMD, plasma lipids, vitamin E (α- and γ-tocopherol, markers of oxidative/nitrative stress (malondialdehyde (MDA and nitro-γ-tocopherol (NGT, and regulators of NO metabolism (arginine (ARG and asymmetric dimethylarginine (ADMA prior to (Pre and immediately following (Post LDL apheresis and at 1, 3, 7, and 14 d Post in 5 hypercholesterolemic patients (52 ± 11 y. Results. Relative to Pre, total cholesterol (7.8±1.5 mmol/L and LDL-cholesterol (6.2±1.2 mmol/L were 61% and 70% lower (P<0.01, respectively, at Post and returned to Pre levels at 14 d. Brachial FMD responses (6.9 ± 3.6% and plasma MDA, ARG, and ADMA concentrations were unaffected by LDL apheresis. Plasma α-tocopherol, γ-tocopherol, and NGT concentrations were 52–69% lower at Post (P<0.01, and α-tocopherol remained 36% lower at 1 d whereas NGT remained 41% lower at d 3. Conclusions. Acute cholesterol reduction by LDL apheresis does not alter VEF, oxidative stress, or NO homeostasis in patients treated chronically for hypercholesterolemia.

  9. Baseline blood pressure, low- and high-density lipoproteins, and triglycerides and the risk of vascular events in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial

    DEFF Research Database (Denmark)

    Amarenco, Pierre; Goldstein, Larry B; Callahan, Alfred

    2009-01-01

    AND RESULTS: The SPARCL trial randomized 4731 patients with recent stroke or transient ischemic attack (TIA) and no known coronary heart disease and LDL-C between 100 and 190 mg/dL to either atorvastatin 80 mg/d or placebo. Baseline assessment included SBP, DBP and measurements of low-density lipoprotein...... associated with MCVE. Atorvastatin treatment was similarly effective regardless of baseline lipoprotein levels....

  10. Social Inclusion Predicts Lower Blood Glucose and Low-Density Lipoproteins in Healthy Adults.

    Science.gov (United States)

    Floyd, Kory; Veksler, Alice E; McEwan, Bree; Hesse, Colin; Boren, Justin P; Dinsmore, Dana R; Pavlich, Corey A

    2017-08-01

    Loneliness has been shown to have direct effects on one's personal well-being. Specifically, a greater feeling of loneliness is associated with negative mental health outcomes, negative health behaviors, and an increased likelihood of premature mortality. Using the neuroendocrine hypothesis, we expected social inclusion to predict decreases in both blood glucose levels and low-density lipoproteins (LDLs) and increases in high-density lipoproteins (HDLs). Fifty-two healthy adults provided self-report data for social inclusion and blood samples for hematological tests. Results indicated that higher social inclusion predicted lower levels of blood glucose and LDL, but had no effect on HDL. Implications for theory and practice are discussed.

  11. Oxidized Low-density Lipoprotein (ox-LDL) Cholesterol Induces the Expression of miRNA-223 and L-type Calcium Channel Protein in Atrial Fibrillation

    Science.gov (United States)

    He, Fengping; Xu, Xin; Yuan, Shuguo; Tan, Liangqiu; Gao, Lingjun; Ma, Shaochun; Zhang, Shebin; Ma, Zhanzhong; Jiang, Wei; Liu, Fenglian; Chen, Baofeng; Zhang, Beibei; Pang, Jungang; Huang, Xiuyan; Weng, Jiaqiang

    2016-08-01

    Atrial fibrillation (AF) is the most common sustained arrhythmia causing high morbidity and mortality. While changing of the cellular calcium homeostasis plays a critical role in AF, the L-type calcium channel α1c protein has suggested as an important regulator of reentrant spiral dynamics and is a major component of AF-related electrical remodeling. Our computational modeling predicted that miRNA-223 may regulate the CACNA1C gene which encodes the cardiac L-type calcium channel α1c subunit. We found that oxidized low-density lipoprotein (ox-LDL) cholesterol significantly up-regulates both the expression of miRNA-223 and L-type calcium channel protein. In contrast, knockdown of miRNA-223 reduced L-type calcium channel protein expression, while genetic knockdown of endogenous miRNA-223 dampened AF vulnerability. Transfection of miRNA-223 by adenovirus-mediated expression enhanced L-type calcium currents and promoted AF in mice while co-injection of a CACNA1C-specific miR-mimic counteracted the effect. Taken together, ox-LDL, as a known factor in AF-associated remodeling, positively regulates miRNA-223 transcription and L-type calcium channel protein expression. Our results implicate a new molecular mechanism for AF in which miRNA-223 can be used as an biomarker of AF rheumatic heart disease.

  12. UVB-induced photoperoxidation of lipids of human low and high density lipoproteins. A possible role of tryptophan residues

    International Nuclear Information System (INIS)

    Salmon, S.; Maziere, J.C.; Santus, R.; Bouchemal, N.; Morliere, P.

    1990-01-01

    Ultraviolet radiation of the UVB region readily destroys tryptophan (Trp) residues of low (LDL) and high (HDL) density lipoproteins. The photooxidation of tryptophan residues is accompanied by peroxidation of low and high density lipoproteins unsaturated fatty acids, as measured by thiobarbituric acid assay. Moreover, low and high density lipoproteins are natural carriers of vitamin E and carotenoids. These two antioxidants are also rapidly bleached by UVB. The UVA radiation promotes neither tryptophan residue destruction nor lipid photoperoxidation. The redox cycling Cu 2+ ions considerably increase lipid photoperoxidation. The synergistic action of photo and auto (Cu 2+ -induced) peroxidation induces marked post-irradiation modifications of apolipoproteins as illustrated by degradation of most tryptophan residues after overnight incubation in the dark of pre-irradiated samples. (author)

  13. Overexpression of porcine lipoprotein-associated phospholipase A2 in swine

    NARCIS (Netherlands)

    Tang, Xiaochun; Wang, Gangqi; Liu, Xingxing; Han, Xiaolei; Li, Zhuang; Ran, Guangyao; Li, Zhanjun; Song, Qi; Ji, Y; Wang, Haijun; Wang, Yuhui; Ouyang, Hongsheng; Pang, Daxin

    2015-01-01

    Lipoprotein-associated phospholipase A 2 (Lp-PLA2) is associated with the risk of vascular disease. It circulates in human blood predominantly in association with low-density lipoprotein cholesterol (LDL-C) and hydrolyses oxidized phospholipids into pro-inflammatory products. However, in the mouse

  14. Corn oil improves the plasma lipoprotein lipid profile compared with extra-virgin olive oil consumption in men and women with elevated cholesterol: results from a randomized controlled feeding trial.

    Science.gov (United States)

    Maki, Kevin C; Lawless, Andrea L; Kelley, Kathleen M; Kaden, Valerie N; Geiger, Constance J; Dicklin, Mary R

    2015-01-01

    Restricted intakes of saturated and trans-fatty acids is emphasized in heart-healthy diets, and replacement with poly- and monounsaturated fatty acids is encouraged. To compare the effects of polyunsaturated fatty acid-rich corn oil (CO) and monounsaturated fatty acid-rich extra-virgin olive oil (EVOO) on plasma lipids in men and women (N = 54) with fasting low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and consumption away from the clinic. Baseline mean (standard error) lipids in mg/dL were: LDL-C 153.3 (3.5), total cholesterol (total-C) 225.7 (3.9), non-high-density lipoprotein (non-HDL)-C 178.3 (3.7), HDL-C 47.4 (1.7), total-C/HDL-C 5.0 (0.2), and TG 124.8 (7.2). CO resulted in significantly larger least-squares mean % changes (all P Consumption of CO in a weight-maintenance, low saturated fat and cholesterol diet resulted in more favorable changes in LDL-C and other atherogenic lipids vs EVOO. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  15. Effect of chromium chloride supplementation on glucose tolerance and serum lipids including high-density lipoprotein of adult men.

    Science.gov (United States)

    Riales, R; Albrink, M J

    1981-12-01

    Chromium deficiency may cause insulin resistance, hyperinsulinemia, impaired glucose tolerance, and hyperlipidemia, recovered by chromium supplementation. The effect of chromium supplementation on serum lipids and glucose tolerance was tested in a double-blind 12-wk study of 23 healthy adult men aged 31 to 60 yr. Either 200 micrograms trivalent chromium in 5 ml water (Cr) or 5 ml plain water (W) was ingested daily 5 days each week. Half the subjects volunteered for glucose tolerance tests with insulin levels. At 12 wk high-density lipoprotein cholesterol increased in the Cr group from 35 to 39 mg/dl (p less than 0.05) but did not change in the water group (34 mg/dl). The largest increase in high-density lipoprotein cholesterol and decreases in insulin and glucose were found in those subjects having normal glucose levels together with elevated insulin levels at base-line. The data are thus consistent with the hypothesis that Cr supplementation raises high-density lipoprotein cholesterol and improves insulin sensitivity in those with evidence of insulin resistance but normal glucose tolerance.

  16. SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jorge L. Gutierrez-Pajares

    2016-10-01

    Full Text Available Studies have demonstrated the significant role of cholesterol and lipoprotein metabolism in the progression of cancer. The SCARB1 gene encodes the scavenger receptor class B type I (SR-BI, which is an 82-kDa glycoprotein with two transmembrane domains separated by a large extracellular loop. SR-BI plays an important role in the regulation of cholesterol exchange between cells and high-density lipoproteins. Accordingly, hepatic SR-BI has been shown to play an essential role in the regulation of the reverse cholesterol transport pathway, which promotes the removal and excretion of excess body cholesterol. In the context of atherosclerosis, SR-BI has been implicated in the regulation of intracellular signaling, lipid accumulation, foam cell formation, and cellular apoptosis. Furthermore, since lipid metabolism is a relevant target for cancer treatment, recent studies have focused on examining the role of SR-BI in this pathology. While signaling pathways have initially been explored in non-tumoral cells, studies with cancer cells have now demonstrated SR-BI’s function in tumor progression. In this review, we will discuss the role of SR-BI during tumor development and malignant progression. In addition, we will provide insights into the transcriptional and post-transcriptional regulation of the SCARB1 gene. Overall, studying the role of SR-BI in tumor development and progression should allow us to gain useful information for the development of new therapeutic strategies.

  17. Moderate doses of alcoholic beverages with dinner and postprandial high density lipoprotein composition

    NARCIS (Netherlands)

    Hendriks, H.F.J.; Veenstra, J.; Tol, A. van; Groener, J.E.M.; Schaafsma, G.

    1998-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. In this study, postprandial changes in plasma lipids, high-density lipoprotein (HDL) composition and cholesteryl ester transfer protein (CETP) and lecithin: cholesterol acyltransferase (LCAT) activity levels

  18. Emerging roles of the intestine in control of cholesterol metabolism

    NARCIS (Netherlands)

    Kruit, Janine-K.; Groen, Albert K.; van Berkel, Theo J.; Kuipers, Folkert

    2006-01-01

    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis, clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor

  19. Dietary Rhus coriaria L. powder reduces the blood cholesterol ...

    African Journals Online (AJOL)

    Dietary Rhus coriaria L. powder reduces the blood cholesterol, VLDL-c and ... of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL-c), low ... birds had higher feed conversion ratio compared with birds in the other treatments.

  20. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  1. HYPOLIPEMIC THERAPY AND LOW SERUM CHOLESTEROL CONCENTRATION

    Directory of Open Access Journals (Sweden)

    Vladmila Bojanic

    2004-01-01

    Full Text Available Low concentration of plasma lipoproteins (hypolipoproteinemia presents decreasing concentrations of all or particular lipids components. Classification of hypolipoproteinemia (hypoLP divides them into: primary (hereditary and secondary. Primary hipoLP are rare diseases and their main characteristic is disorder of apolipoproteins synthesis, which leads to low serum cholesterol concentration. Secondary hipoLP are presented in many diseases. They have diagnostic, prognostic significance and present good therapeutic marker. However, modern therapeutic approaches for aggressive lipid lowering pointed out many questions about physiological limits for cholesterol lowering. These approaches, also, open many questions about consequences of low serum concentration of total cholesterol and triglicerides.

  2. Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <130 mg/dL (AIDS Clinical Trials Group Study A5275).

    Science.gov (United States)

    Nixon, Daniel E; Bosch, Ronald J; Chan, Ellen S; Funderburg, Nicholas T; Hodder, Sally; Lake, Jordan E; Lederman, Michael M; Klingman, Karin L; Aberg, Judith A

    Persistent immune activation and inflammation in virologically suppressed human immunodeficiency virus (HIV) infection are linked to excess cardiovascular risk. To evaluate atorvastatin as a strategy to reduce cardiovascular risk. A5275 was a multicenter, prospective, randomized, double-blind, placebo-controlled, cross-over pilot study of atorvastatin (10 mg/day for 4 weeks then 20 mg/day for 16 weeks) with a planned enrollment of 97 HIV-infected participants ≥18 years old, receiving boosted protease inhibitor-based antiretroviral therapy for ≥6 months, with plasma HIV-1 RNAs below limits of quantification ≥180 days, and fasting low-density lipoprotein (LDL) cholesterol ≥70 and atorvastatin treatment. Analyses were as-treated. Ninety-eight participants were enrolled at 31 U S sites and 73 completed study treatment. Atorvastatin treatment did not decrease T-lymphocyte or monocyte activation, circulating biomarker levels (interleukin-6, D-dimer, soluble CD14, soluble CD163, monocyte chemoattractant protein-1, interferon-gamma-induced protein-10, high-sensitivity C-reactive protein, CD40L, and P-selectin) or white blood cell Krüppel-like Factor 2/4 messenger RNA levels. Pre-to-post atorvastatin reductions in calculated LDL (-38%), oxidized-LDL (-33%), and lipoprotein-associated phospholipase A2 (-31%) were significant (P atorvastatin did not significantly decrease levels of soluble or cellular biomarkers of immune activation and inflammation but resulted in robust reductions in LDL cholesterol, oxLDL, and lipoprotein-associated phospholipase A 2 , biomarkers associated with cardiovascular risk. Copyright © 2016 National Lipid Association. All rights reserved.

  3. High-Density Lipoprotein Cholesterol Level Relates to Working Memory, Immediate and Delayed Cued Recall in Brazilian Older Adults: The Role of Cognitive Reserve.

    Science.gov (United States)

    Ihle, Andreas; Gouveia, Élvio R; Gouveia, Bruna R; Freitas, Duarte L; Jurema, Jefferson; Tinôco, Maria A; Kliegel, Matthias

    2017-01-01

    The present study set out to investigate the relation of the high-density lipoprotein cholesterol (HDL-C) level to cognitive performance and its interplay with key markers of cognitive reserve in a large sample of older adults. We assessed tests of working memory, immediate and delayed cued recall in 701 older adults from Amazonas, Brazil. The HDL-C level was derived from fasting blood samples. In addition, we interviewed individuals on their education, past occupation, and cognitive leisure activity. A critically low HDL-C level (cued recall. Moderation analyses suggested that the relations of the HDL-C level to working memory and delayed cued recall were negligible in individuals with longer education, a higher cognitive level of the job, and greater engagement in cognitive leisure activity. Cognitive reserve accumulated during the life course may reduce the detrimental influences of a critically low HDL-C level on cognitive functioning in old age. © 2017 S. Karger AG, Basel.

  4. Low density lipoprotein sensor based on surface plasmon resonance

    International Nuclear Information System (INIS)

    Matharu, Zimple; Sumana, G.; Pandey, M.K.; Gupta, Vinay; Malhotra, B.D.

    2009-01-01

    Biotinylated heparin has been immobilized onto self-assembled monolayer of 4-aminothiophenol using avidin-biotin specific binding. The modified electrodes have been characterized using surface plasmon resonance technique (SPR), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM) and contact angle (CA) measurements. The interaction of immobilized biotinylated heparin with low density lipoprotein (LDL) has been studied using surface plasmon resonance technique. The biotinylated heparin modified electrode can be used to detect LDL in the range of 20 to 100 mg/dl with the sensitivity of 513.3 m o /μM.

  5. Low density lipoprotein sensor based on surface plasmon resonance

    Energy Technology Data Exchange (ETDEWEB)

    Matharu, Zimple [Department of Science and Technology Centre on Biomolecular Electronics, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Department of Physics and Astrophysics, University of Delhi, New Delhi-110007 (India); Sumana, G.; Pandey, M.K. [Department of Science and Technology Centre on Biomolecular Electronics, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Gupta, Vinay [Department of Physics and Astrophysics, University of Delhi, New Delhi-110007 (India); Malhotra, B.D., E-mail: bansi.malhotra@gmail.co [Department of Science and Technology Centre on Biomolecular Electronics, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India)

    2009-11-30

    Biotinylated heparin has been immobilized onto self-assembled monolayer of 4-aminothiophenol using avidin-biotin specific binding. The modified electrodes have been characterized using surface plasmon resonance technique (SPR), cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), atomic force microscopy (AFM) and contact angle (CA) measurements. The interaction of immobilized biotinylated heparin with low density lipoprotein (LDL) has been studied using surface plasmon resonance technique. The biotinylated heparin modified electrode can be used to detect LDL in the range of 20 to 100 mg/dl with the sensitivity of 513.3 m{sup o}/{mu}M.

  6. EFFECT OF ADIPOSITY ON PLASMA-LIPID TRANSFER PROTEIN ACTIVITIES - A POSSIBLE LINK BETWEEN INSULIN-RESISTANCE AND HIGH-DENSITY-LIPOPROTEIN METABOLISM

    NARCIS (Netherlands)

    DULLAART, RPF; SLUITER, WJ; DIKKESCHEI, LD; HOOGENBERG, K; VANTOL, A

    The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of

  7. Changes in remnant and high-density lipoproteins associated with hormone therapy and progression of coronary artery disease in postmenopausal women

    Science.gov (United States)

    The effect of hormone therapy (HT) on the plasma concentration of remnant lipoprotein cholesterol (RLP-C) and high density lipoprotein (HDL) subpopulations and the contribution of HT-related changes in these lipoproteins to the progression of coronary heart disease (CHD) were examined in 256 postmen...

  8. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz

    2015-01-01

    BACKGROUND: Observational studies in older subjects have shown no or inverse associations between cholesterol levels and mortality. However, in old age plasma low-density lipoprotein cholesterol (LDL-C) may not reflect the lifetime level due to reverse causality, and hence the risk may...

  9. Serum lipoprotein (a) concentration in patients with nephrotic syndrome and its clinical implication.

    Science.gov (United States)

    Yang, X; Wang, H; Zhu, Z; Deng, A

    1998-01-01

    Serum lipoprotein(a) [Lp(a)] concentration was determined in 42 patients with primary nephrotic syndrome (NS) and the relationships between Lp (a) and plasma lipids, apolipoproteins, serum creatinine (Scr), albumin, urinary proteins (Upro) were also analyzed. The results showed that: (1) serum Lp(a) concentrations in the patients with NS were higher than those in healthy controls; (2) the levels of serum Lp(a) were correlated positively with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein B (Apo-B), Upros (Upro). It is concluded that the NS patients had the potential risk of suffering from coronary artery disease, glomerular sclerosis and thrombosis. The remission of NS may partially decrease the serum Lp(a) levels. Further studies are needed to explore the prevention and treatment of dislipedemia in patients with NS.

  10. miRNA regulation of LDL-cholesterol metabolism.

    Science.gov (United States)

    Goedeke, Leigh; Wagschal, Alexandre; Fernández-Hernando, Carlos; Näär, Anders M

    2016-12-01

    In the past decade, microRNAs (miRNAs) have emerged as key regulators of circulating levels of lipoproteins. Specifically, recent work has uncovered the role of miRNAs in controlling the levels of atherogenic low-density lipoprotein LDL (LDL)-cholesterol by post-transcriptionally regulating genes involved in very low-density lipoprotein (VLDL) secretion, cholesterol biosynthesis, and hepatic LDL receptor (LDLR) expression. Interestingly, several of these miRNAs are located in genomic loci associated with abnormal levels of circulating lipids in humans. These findings reinforce the interest of targeting this subset of non-coding RNAs as potential therapeutic avenues for regulating plasma cholesterol and triglyceride (TAG) levels. In this review, we will discuss how these new miRNAs represent potential pre-disposition factors for cardiovascular disease (CVD), and putative therapeutic targets in patients with cardiometabolic disorders. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Assessing the functional properties of high-density lipoproteins : an emerging concept in cardiovascular research

    NARCIS (Netherlands)

    Triolo, Michela; Annema, Wijtske; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    Although plasma concentrations of high-density lipoprotein (HDL) cholesterol correlate inversely with the incidence of atherosclerotic cardiovascular disease, results from recent epidemiological, genetic and pharmacological intervention studies resulted in a shift of concept. Rather than HDL

  12. L-Cysteine-induced up-regulation of the low-density lipoprotein receptor is mediated via a transforming growth factor-alpha signalling pathway.

    Science.gov (United States)

    Tanaka, Yuma; Shimada, Masaya; Nagaoka, Satoshi

    2014-02-14

    Sulphur-containing amino acids regulate plasma cholesterol levels in animals and humans. However, their mechanism of action remains unclear. Low-density lipoprotein receptor (LDLR) plays an important role in cholesterol metabolism. We therefore investigated the effects of sulphur-containing amino acids on the expression of LDLR in hepatocytes. HepG2 cells were cultured in Dulbecco's Modified Eagle's Medium with or without sulphur-containing amino acids and cysteine-containing compounds. We found that L-cysteine increased LDLR mRNA and enhanced LDLR gene promoter activity through the extracellular-signal-related kinase and p38 mitogen-activated protein kinase signalling pathways in HepG2 cells. Moreover, we observed that L-cysteine stimulated the release of transforming growth factor-alpha (TGF-α) and that TGF-α increased the LDLR mRNA levels. This study provides a report of the L-cysteine mediated up-regulation of the LDLR expression via TGF-α signalling pathway. Our findings provide insights into cholesterol homeostasis and amino acid signalling. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Direct effects of fatty meals and adiposity on oxidised low-density lipoprotein.

    Science.gov (United States)

    Laguna-Camacho, Antonio; Alonso-Barreto, Arely S; Mendieta-Zerón, Hugo

    2015-01-01

    High-fat intake and high adiposity contribute to hyperlipaemia. In a hyperlipaemic state, lipoproteins infiltrate arterial wall where they are modified and cause an immune response characteristic of atherosclerosis. A small fraction of modified lipoproteins including oxidised low-density lipoprotein (ox-LDL) returns to circulation. The present study tracked high-fat meals during four weeks as to find effects of sustained frequency change on adiposity and ox-LDL. The findings indicated that changes in frequency of consumption of high-fat eating episodes correlated directly with changes in adiposity and ox-LDL. Hence the number of fatty meals consumed by people with overweight or obesity in few weeks could affect the atherogenic process. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

  14. Nonlinear associations between plasma cholesterol levels and neuropsychological function.

    Science.gov (United States)

    Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

    2016-11-01

    Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  15. Investigations on the transport and metabolism of high density lipoprotein cholesteryl esters in African green monkeys

    International Nuclear Information System (INIS)

    Sorci-Thomas, M.G.

    1984-01-01

    The metabolic fate of circulating high density lipoprotein cholesteryl esters was studied in African green monkeys to determine the significance of the lipid transfer reaction on the catabolism of lipoprotein cholesteryl esters. A method of doubly labeling both moieties of lipoprotein cholesteryl esters with [ 3 He]cholesteryl oleate and cholesteryl [ 14 C]oleate was developed for the purpose of studying plasma cholesteryl ester metabolism in vivo. In these studies the total plasma [ 3 He]cholesterol turnover resulted in production rates, which ranged from 10-17 mg/kg day, similar to previously reported values in African green monkeys and in normal lipoproteinemic humans. In contrast to the production rates calculated from the decay of plasma 3 He-radioactivity, the production rates calculated from lipoproteins labeled with cholesteryl [ 14 C]oleate were approximately 2-3 times greater. In addition to these studies, a plasma cholesteryl ester transacylation activity was demonstrated in vitro when HDL containing doubly labeled cholesteryl esters were incubated with fresh plasma. These results demonstrated that high density lipoprotein cholesteryl esters undergo transacylation in vitro, resulting in release and reesterification of free [ 3 H]cholesterol

  16. Effects of estrogen on very low-density lipoprotein triglyceride metabolism in fed and fasted chicks

    International Nuclear Information System (INIS)

    Park, J.R.

    1988-01-01

    A single injection of estrogen into growing chicks resulted in a marked elevation in plasma triglyceride (TG) followed by phospholipid (PL) and cholesterol (CH) in both fed and fasted chicks. Estrogen caused a development of massive fatty liver in fed chicks. Hepatic malic enzyme and glucose-6-phosphate dehydrogenase activities also increased significantly in fed chicks and, to a small extent, in fasted chicks. Very low density lipoproteins (VLDL) were barely detectable in the fasted control plasma. However, the VLDL concentration increased markedly upon estrogen injection, becoming the most prevalent lipoprotein in the plasma. The administration of estrogen resulted in an increase in oleic acid and a decrease in linoleic acid content except in the cholesteryl ester of VLDL and LDL. VLDL of estrogenized birds had β-mobility on agarose gel electrophoresis, and they eluted in two peaks on agarose gel filtration chromatography. Both peaks on gel filtration exhibited the same β-mobility on agarose gel electrophoresis. Nevertheless, the apoprotein composition of these two peaks were substantially different from each other; apo B was not present in the first peak VLDL. VLDL-TG kinetic studies conducted in vivo, using 14 C-TG-VLDL prepared endogenously from control and estrogenized chicks revealed that VLDL-TG produced from the former had a higher fractional catabolic rate (FCR) than VLDL-TG from the latter

  17. Inhibition of fatty acid synthesis decreases very low density lipoprotein secretion in the hamster.

    Science.gov (United States)

    Arbeeny, C M; Meyers, D S; Bergquist, K E; Gregg, R E

    1992-06-01

    The hamster was developed as a model to study very low density lipoprotein (VLDL) metabolism, since, as is the case in humans, the hamster liver was found to synthesize apoB-100 and not apoB-48. The effect of inhibiting fatty acid synthesis on the hepatic secretion of VLDL triglyceride (TG) and apolipoprotein (apo) B-100 in this model was then investigated. In an in vivo study, hamsters were fed a chow diet containing 0.15% TOFA (5-tetradecyloxy-2-furancarboxylic acid), an inhibitor of acetyl-CoA carboxylase. After 6 days of treatment, plasma triglyceride and cholesterol levels were decreased by 30.2% and 11.6%, respectively. When the secretion of VLDL-TG by the liver was measured in vivo after injection of Triton WR 1339, TOFA treatment was found to decrease VLDL-TG secretion by 40%. In subsequent in vitro studies utilizing cultured primary hamster hepatocytes, incubation with 20 microM TOFA for 4 h resulted in 98% and 76% inhibition in fatty acid and triglyceride synthesis, respectively; VLDL-TG secretion was decreased by 90%. When hepatocytes were pulsed with [3H]leucine, incubation with TOFA resulted in a 50% decrease in the incorporation of radiolabel into secreted VLDL apoB-100. The results of this study indicate that inhibition of intracellular triglyceride synthesis decreases the secretion of VLDL-TG and apoB-100, and does not result in the secretion of a dense, triglyceride-depleted lipoprotein.

  18. Identification of the Oxidized Low-Density Lipoprotein Scavenger Receptor CD36 in Plasma

    DEFF Research Database (Denmark)

    Handberg, Aase; Levin, Klaus; Højlund, Kurt

    2006-01-01

    BACKGROUND: Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature...

  19. MooPoong (Gye Young Jeong) increases HDL-cholesterol but decreases LDL cholesterol and body-weight.

    Science.gov (United States)

    Chung, Hwan-Suck; Hong, Seung-Heon; Do, Keum-Rok; Rhee, Hyung-Koo; Jung, Sung-Ki; Hwang, Woo-Jun; Kim, Hyung-Min

    2004-05-01

    MooPoong (MP, Gye Young Jeong), a Korean traditional wine, has been used as a prevention and treatment agent of blood circulatory trouble. To evaluate such an effect of MP, we analyzed whether the plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body weight change after rats were fed on high fat diet with MP for 8 weeks. Plasma LDL cholesterol level decreased by 5.6% in 0.128% MP treated group and by 11.1% in 0.640% MP treated group. However, HDL cholesterol was increased by 6.7% in 0.128% MP diet group and 33.3% in 0.640% MP diet group. In addition, there was a significant weight loss in the MP treated group compared with the high-fat diet group (P < 0.05). Our findings indicate that MP may contain compounds with actions which can treat blood circulatory trouble as well as overweight.

  20. CRISPR Correction of a Homozygous Low-Density Lipoprotein Receptor Mutation in Familial Hypercholesterolemia Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Omer, Linda; Hudson, Elizabeth A; Zheng, Shirong; Hoying, James B; Shan, Yuan; Boyd, Nolan L

    2017-11-01

    Familial hypercholesterolemia (FH) is a hereditary disease primarily due to mutations in the low-density lipoprotein receptor (LDLR) that lead to elevated cholesterol and premature development of cardiovascular disease. Homozygous FH patients (HoFH) with two dysfunctional LDLR alleles are not as successfully treated with standard hypercholesterol therapies, and more aggressive therapeutic approaches to control cholesterol levels must be considered. Liver transplant can resolve HoFH, and hepatocyte transplantation has shown promising results in animals and humans. However, demand for donated livers and high-quality hepatocytes overwhelm the supply. Human pluripotent stem cells can differentiate to hepatocyte-like cells (HLCs) with the potential for experimental and clinical use. To be of future clinical use as autologous cells, LDLR genetic mutations in derived FH-HLCs need to be corrected. Genome editing technology clustered-regularly-interspaced-short-palindromic-repeats/CRISPR-associated 9 (CRISPR/Cas9) can repair pathologic genetic mutations in human induced pluripotent stem cells. We used CRISPR/Cas9 genome editing to permanently correct a 3-base pair homozygous deletion in LDLR exon 4 of patient-derived HoFH induced pluripotent stem cells. The genetic correction restored LDLR-mediated endocytosis in FH-HLCs and demonstrates the proof-of-principle that CRISPR-mediated genetic modification can be successfully used to normalize HoFH cholesterol metabolism deficiency at the cellular level.

  1. Human Lipoproteins at Model Cell Membranes

    DEFF Research Database (Denmark)

    Browning, K L; Lind, T K; Maric, S

    2017-01-01

    High and low density lipoproteins (HDL and LDL) are thought to play vital roles in the onset and development of atherosclerosis; the biggest killer in the western world. Key issues of initial lipoprotein (LP) interactions at cellular membranes need to be addressed including LP deposition and lipid...... exchange. Here we present a protocol for monitoring the in situ kinetics of lipoprotein deposition and lipid exchange/removal at model cellular membranes using the non-invasive, surface sensitive methods of neutron reflection and quartz crystal microbalance with dissipation. For neutron reflection, lipid...... support the notion of HDL acting as the 'good' cholesterol, removing lipid material from lipid-loaded cells, whereas LDL acts as the 'bad' cholesterol, depositing lipid material into the vascular wall....

  2. Low-density lipoprotein apheresis: an evidence-based analysis.

    Science.gov (United States)

    2007-01-01

    To assess the effectiveness and safety of low-density lipoprotein (LDL) apheresis performed with the heparin-induced extracorporeal LDL precipitation (HELP) system for the treatment of patients with refractory homozygous (HMZ) and heterozygous (HTZ) familial hypercholesterolemia (FH). BACKGROUND ON FAMILIAL HYPERCHOLESTEROLEMIA: Familial hypercholesterolemia is a genetic autosomal dominant disorder that is caused by several mutations in the LDL-receptor gene. The reduced number or absence of functional LDL receptors results in impaired hepatic clearance of circulating low-density lipoprotein cholesterol (LDL-C) particles, which results in extremely high levels of LDL-C in the bloodstream. Familial hypercholesterolemia is characterized by excess LDL-C deposits in tendons and arterial walls, early onset of atherosclerotic disease, and premature cardiac death. Familial hypercholesterolemia occurs in both HTZ and HMZ forms. Heterozygous FH is one of the most common monogenic metabolic disorders in the general population, occurring in approximately 1 in 500 individuals. Nevertheless, HTZ FH is largely undiagnosed and an accurate diagnosis occurs in only about 15% of affected patients in Canada. Thus, it is estimated that there are approximately 3,800 diagnosed and 21,680 undiagnosed cases of HTZ FH in Ontario. In HTZ FH patients, half of the LDL receptors do not work properly or are absent, resulting in plasma LDL-C levels 2- to 3-fold higher than normal (range 7-15mmol/L or 300-500mg/dL). Most HTZ FH patients are not diagnosed until middle age when either they or one of their siblings present with symptomatic coronary artery disease (CAD). Without lipid-lowering treatment, 50% of males die before the age of 50 and 25% of females die before the age of 60, from myocardial infarction or sudden death. In contrast to the HTZ form, HMZ FH is rare (occurring in 1 case per million persons) and more severe, with a 6- to 8-fold elevation in plasma LDL-C levels (range 15-25mmol

  3. Secondary prevention care and effect: Total and low-density lipoprotein cholesterol levels and lipid-lowering drug use in women and men after incident myocardial infarction - The Tromsø Study 1994-2016.

    Science.gov (United States)

    Hopstock, Laila A; Eggen, Anne Elise; Løchen, Maja-Lisa; Mathiesen, Ellisiv B; Njølstad, Inger; Wilsgaard, Tom

    2018-02-01

    Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. We followed 10,005 participants (54% women) attending the Tromsø Study 1994-1995 and 8483 participants (55% women) attending the Tromsø Study 2007-2008 for first-ever MI up to their participation in 2007-2008 and 2015-2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994-2008 and 2007-2013, respectively. Mean change in total cholesterol was -2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was -1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was -0.33 (95% confidence interval [CI] -0.51 to -0.14) for total cholesterol and -0.21 (95% CI -0.37 to -0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15-2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.

  4. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  5. Lipoprotein distribution and serum concentrations of 7α-hydroxy-4-cholesten-3-one and bile acids: effects of monogenic disturbances in high-density lipoprotein metabolism

    DEFF Research Database (Denmark)

    Steiner, Carine; Holleboom, Adriaan G; Karuna, Ratna

    2012-01-01

    BA (bile acid) formation is considered an important final step in RCT (reverse cholesterol transport). HDL (high-density lipoprotein) has been reported to transport BAs. We therefore investigated the effects of monogenic disturbances in human HDL metabolism on serum concentrations and lipoprotein...... concentrations of conjugated and secondary BAs differed between heterozygous carriers of SCARB1 (scavenger receptor class B1) mutations and unaffected individuals (P...

  6. The Impact of Cardiorespiratory Fitness on Age-Related Lipids and Lipoproteins

    Science.gov (United States)

    Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F.; Lavie, Carl J.; Hardin, James W.; Blair, Steven N.

    2015-01-01

    Background Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. Objectives This study sought to assess the longitudinal, aging trajectory of lipids and lipoproteins for the life course in adults, and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Methods Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 (mean 3.5) health examinations between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Results Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until the mid-40s to early 50s, with subsequent declines (all p lipoproteins in young to middle-aged men than in older men. Conclusions Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men, and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. PMID:25975472

  7. The effect of cardiorespiratory fitness on age-related lipids and lipoproteins.

    Science.gov (United States)

    Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F; Lavie, Carl J; Hardin, James W; Blair, Steven N

    2015-05-19

    Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. This study sought to assess the longitudinal aging trajectory of lipids and lipoproteins for the life course in adults and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 health examinations (mean 3.5 examinations) between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until age mid-40s to early 50s, with subsequent declines (all p lipoproteins in young to middle-age men than in older men. Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Blood Lipoproteins under the Action of Exogenous Sex Steroids in the Postresuscitation Period

    Directory of Open Access Journals (Sweden)

    L. N. Shcherbakova

    2011-01-01

    Full Text Available Objective: to study the effect of reproductive hormones on the blood lipoprotein spectrum in the postresuscitation period after cardiac arrest. Materials and methods. Experiments were carried out on 66 mature albino rats of either sex weighing 200—250 g. Ten-minute cardiac arrest was induced by intrathoracic ligation of the vascular bundle. At 30 min after resuscitation, 49 animals were intramuscularly injected placebo and 17 animals were administered gyn-odian depot (Schering, Germany. The investigators measured the plasma concentrations of progesterone, 17-OH progesterone, androstenedione, dehydroepiandrosterone sulfate, testosterone, estradiol, and estriol, as well as the levels of triglycerides, total, and high-density lipoprotein (HDL, low-density lipoprotein (LDL, and very low-density lipoprotein (VLDL cholesterols. Blood was sampled on days 2 and 16 in the absence of therapy and on day 16 of sex steroid therapy. Results. By day 2 postresuscitation, the progesterone/estradiol ratio increased by approximately 1.8 times in males and females. Despite the fact that there were no changes in the concentrations of triglycerides, VLDL and HDL cholesterols in both males and females at that time, but the level of LDL cholesterol increased. Gender-related differences in the LDL spectrum by day 2 postresuscitation remained only in the levels of LDL cholesterol. Despite the normalization of progesterone levels, the concentrations of triglycerides and VLDL cholesterol decreased by day 16 of the postresuscitative period in the absence of therapy. There were no gender-related differences in the lipoprotein spectrum at this stage. The exogenous estradiol in combination with dehydroepiandrosterone caused a significant increase in the concentration of HLD cholesterol and a reduction in that of VLDL cholesterol in males and females both. Conclusion. Under gynodian action, the lipid spectrum was indicative of the exogenous estra-diol and

  9. Reference values assessment in a Mediterranean population for small dense low-density lipoprotein concentration isolated by an optimized precipitation method

    Directory of Open Access Journals (Sweden)

    Fernández-Cidón B

    2017-06-01

    Full Text Available Bárbara Fernández-Cidón,1–3 Ariadna Padró-Miquel,1 Pedro Alía-Ramos,1 María José Castro-Castro,1 Marta Fanlo-Maresma,4 Dolors Dot-Bach,1 José Valero-Politi,1 Xavier Pintó-Sala,4 Beatriz Candás-Estébanez1 1Clinical Laboratory, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain; 2Department of Biochemistry, Molecular Biology and Biomedicine, Autonomous University of Barcelona (UAB, Barcelona, Spain; 3Department of Pharmacotherapy, Pharmacogenetics and Pharmaceutical Technology, Institut d’Investigació Biomèdica de Bellvitge (IDIBELL, L’Hospitalet de Llobregat, Spain; 4Cardiovascular Risk Unit, Hospital Universitari de Bellvitge, L’Hospitalet de Llobregat, Spain Background: High serum concentrations of small dense low-density lipoprotein cholesterol (sd-LDL-c particles are associated with risk of cardiovascular disease (CVD. Their clinical application has been hindered as a consequence of the laborious current method used for their quantification. Objective: Optimize a simple and fast precipitation method to isolate sd-LDL particles and establish a reference interval in a Mediterranean population. Materials and methods: Forty-five serum samples were collected, and sd-LDL particles were isolated using a modified heparin-Mg2+ precipitation method. sd-LDL-c concentration was calculated by subtracting high-density lipoprotein cholesterol (HDL-c from the total cholesterol measured in the supernatant. This method was compared with the reference method (ultracentrifugation. Reference values were estimated according to the Clinical and Laboratory Standards Institute and The International Federation of Clinical Chemistry and Laboratory Medicine recommendations. sd-LDL-c concentration was measured in serums from 79 subjects with no lipid metabolism abnormalities. Results: The Passing–Bablok regression equation is y = 1.52 (0.72 to 1.73 + 0.07x (−0.1 to 0.13, demonstrating no significant statistical differences

  10. Transvascular low-density lipoprotein transport in patients with diabetes mellitus (type 2)

    DEFF Research Database (Denmark)

    Kornerup, Karen; Nordestgaard, Børge Grønne; Feldt-Rasmussen, Bo

    2002-01-01

    accumulation and, thus, atherosclerosis. METHODS AND RESULTS: We developed an in vivo method for measurement of transvascular transport of low density lipoprotein (LDL) and applied it in 16 patients with maturity-onset diabetes (type 2) and 29 healthy control subjects. Autologous 131I-labeled LDL...... plasma insulin levels in diabetic patients. CONCLUSIONS: Transvascular LDL transport may be increased in patients with type 2 diabetes. This suggests that lipoprotein flux into the arterial wall is increased in people with diabetes, possibly explaining the accelerated development of atherosclerosis....... in patients with diabetes and control subjects, respectively (P2.5%/h and 5.3+/-1.6%/h (P

  11. Serum lipid and lipoprotein concentrations following exposure to ozone

    Energy Technology Data Exchange (ETDEWEB)

    Vaughan, W J; Adamson, G L; Lindgren, F T; Schooley, J.C.

    1984-07-01

    The effects of exposure to ozone (O/sub 3/) on concentrations of serum lipids and lipoproteins were investigated. Male and female guinea pigs were exposed to O/sub 3/ at 1 ppm for two weeks. Serum concentrations of cholesterol, triglycerides, low density (LDL) and very low density (VLDL) lipoproteins were elevated after O/sub 3/ exposure, particularly in males. During O/sub 3/ exposure the food intake per day decreased (for a constant body weight), suggesting that metabolic rate and possibly basal metabolic rate was lower. Lung wet weights increased during O/sub 3/ exposure by 87% for males and 45% for females. When individual lung weight/body weight ratios were correlated with cholesterol and LDL values from the same animal, a high correlation is found for males (r . 0.81, P less than 0.05), suggesting that there may be a relationship between lipoprotein elevations and lung damage for males. Because elevated concentrations of lipids and lipoproteins in humans increase the risk of coronary heart disease (CHD), the lipoprotein results suggest that an epidemiological study of the incidence of CHD with metropolitan O/sub 3/ levels may be warranted.

  12. Cholesterol Levels: What You Need to Know: MedlinePlus Health Topic

    Science.gov (United States)

    ... lipoprotein ( LDL ) cholesterol and high-density lipoprotein ( HDL ) cholesterol. LDL (bad) cholesterol - the main source of cholesterol buildup ... Teens How to Lower Cholesterol How to Lower Cholesterol with Diet LDL: The "Bad" Cholesterol Nutrition Statins Triglycerides VLDL Cholesterol ...

  13. Consumption of a liquid high-fat meal increases triglycerides but decreases high-density lipoprotein cholesterol in abdominally obese subjects with high postprandial insulin resistance.

    Science.gov (United States)

    Wang, Feng; Lu, Huixia; Liu, Fukang; Cai, Huizhen; Xia, Hui; Guo, Fei; Xie, Yulan; Huang, Guiling; Miao, Miao; Shu, Guofang; Sun, Guiju

    2017-07-01

    Abdominal obesity is associated with an increased risk of insulin resistance, which may be a potential contributor to dyslipidemia. However, the relationship between postprandial insulin resistance and lipid metabolism in abdominally obese subjects remains unknown. We hypothesized that postprandial dyslipidemia would be exaggerated in abdominally obese subjects with high postprandial insulin resistance. To test this hypothesis, serum glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and apolipoprotein B were measured at baseline and postprandial state at 0.5, 1, 2, 4, 6, and 8 hours after a liquid high-fat meal in non-abdominally obese controls (n=44) and abdominally obese subjects with low (AO-LPIR, n=40), middle (n=40), and high postprandial insulin resistance (AO-HPIR, n=40) based on the tertiles ratio of the insulin to glucose areas under the curve (AUC). Their serum adipokines were tested at baseline only. Fasting serum leptin was higher (Pinsulin resistance and controls. The present study indicated that the higher degree of postprandial insulin resistance, the more adverse lipid profiles in abdominally obese subjects, which provides insight into opportunity for screening in health. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

    Science.gov (United States)

    Lamon-Fava, S; Fisher, E C; Nelson, M E; Evans, W J; Millar, J S; Ordovas, J M; Schaefer, E J

    1989-01-01

    Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

  15. HDL cholesterol, LDL receptor activity and response to dietary cholesterol *1 A reply to the letter of Cortese, Miller, Marenah and Lewis [2

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.

    1984-01-01

    Variation in the concentration of cholesterol in blood plasma is partly accounted for by differences in diet, age, sex and genetic constitution. No correlation between plasma low density lipoprotein (LDL) cholesterol concentration and the activity of the LDL receptor in white blood cells could be

  16. Lipoprotein cholesterol uptake mediates upregulation of bile acid synthesis by increasing cholesterol 7a-hydroxylase but not sterol 27- hydroxylase gene expression in cultured rat hepatocytes.

    NARCIS (Netherlands)

    Post, S.M.; Twisk, J.W.R.; van der Fits, L.T.E.; Wit, E.C.M.; Hoekman, M.F.M.; Mager, W.H.; Princen, H.M.G.

    1999-01-01

    Lipoproteins may supply substrate for the formation of bile acids, and the amount of hepatic cholesterol can regulate bile-acid synthesis and increase cholesterol 7α-hydroxylase expression. However, the effect of lipoprotein cholesterol on sterol 27-hydroxylase expression and the role of different

  17. Pitavastatin 4 mg Provides Significantly Greater Reduction in Remnant Lipoprotein Cholesterol Compared With Pravastatin 40 mg: Results from the Short-term Phase IV PREVAIL US Trial in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia.

    Science.gov (United States)

    Miller, P Elliott; Martin, Seth S; Joshi, Parag H; Jones, Steven R; Massaro, Joseph M; D'Agostino, Ralph B; Sponseller, Craig A; Toth, Peter P

    2016-03-01

    Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that are implicated in atherosclerosis. We assessed the adequacy of pitavastatin 4 mg and pravastatin 40 mg in reducing atherogenic lipid parameters beyond LDL-C, in particular remnant lipoprotein cholesterol (RLP-C). From the Phase IV, multicenter, randomized, double-blind PREVAIL US (A Study of Pitavastatin 4 mg Vs. Pravastatin 40 mg in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia) trial, we examined lipoprotein cholesterol subfractions using Vertical Auto Profile testing and apolipoproteins B and A-I at baseline and 12 weeks. Participants with primary hyperlipidemia or mixed dyslipidemia had LDL-C levels of 130 to 220 mg/dL and triglyceride levels ≤ 400 mg/dL. In this post hoc analysis, changes in lipid parameters were compared by using ANCOVA. Lipoprotein subfraction data were available in 312 patients (pitavastatin, n = 157; pravastatin, n = 155). Pitavastatin promoted a greater reduction in RLP-C than pravastatin (-13.6 [8.7] vs -9.3 [9.5] mg/dL). Furthermore, the pitavastatin group reported greater reductions in both components of RLP-C (both, P < 0.001): intermediate-density lipoprotein cholesterol (-9.5 [6.3] vs -6.4 [6.6] mg/dL) and very low-density lipoprotein cholesterol subfraction 3 (-4.1 [3.5] vs -2.9 [3.8] mg/dL). There were also greater reductions in the major ratios of risk (apolipoprotein B/apolipoprotein A-I and total cholesterol/HDL-C) (both, P < 0.001). There were no significant changes in HDL-C, its subfractions, or natural log lipoprotein(a)-cholesterol. The mean age was 58.8 ± 8.9 years in the pitavastatin group and 57.0 ± 10.2 years in the pravastatin group. Compared with pravastatin 40 mg daily, pitavastatin 4 mg provided superior reductions in atherogenic lipid parameters beyond LDL-C, including RLP-C. Future studies are needed investigate the clinical implications of lowering directly measured RLP-C as the principal target. ClinicalTrials.gov identifier

  18. Structure of human low-density lipoprotein subfractions, determined by X-ray small-angle scattering.

    Science.gov (United States)

    Baumstark, M W; Kreutz, W; Berg, A; Frey, I; Keul, J

    1990-01-19

    The structure of low-density lipoprotein (LDL) particles from three different density ranges (LDL-1: d = 1.006-1.031 g/ml; LDL-3: d = 1.034-1.037 g/ml; LDL-6: d = 1.044-1.063 g/ml) was determined by X-ray small-angle scattering. By using a theoretical particle model, which accounted for the polydispersity of the samples, we were able to obtain fits of the scattering intensity that were inside the noise interval of the measured intensity. The assumption of deviations from radial symmetry is not supported by our data. This implies a spread-out conformation of the apolipoprotein B (apoB) molecule, which appears to be localized in the outer surface shell. A globular structure is not consistent with our data. Furthermore, different models exist concerning the structure of the cholesterol ester core below the phase transition temperature. The electron density data suggest an arrangement in which the steroid moieties are localized at average radii of 3.2 and 6.4 nm. Model calculations show that packing problems can only be avoided if approximately half of the acyl chains of each shell are pointing towards the center of the particle, the other half towards the surface. This arrangement of the acyl chains has never been proposed before. The LDL particles of different density classes differ mainly with respect to the size of the core but also with respect to the width of the surface shells. Model calculations show that the size of different LDL particles can be accurately predicted from the compositional data.

  19. Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

    International Nuclear Information System (INIS)

    East, C.; Grundy, S.M.; Bilheimer, D.W.

    1986-01-01

    Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia

  20. Dietary supplementation with d-tagatose in subjects with type 2 diabetes leads to weight loss and raises high-density lipoprotein cholesterol.

    Science.gov (United States)

    Donner, Thomas W; Magder, Laurence S; Zarbalian, Kiarash

    2010-12-01

    Oral d-tagatose (d-tag) attenuates the rise in plasma glucose during an oral glucose tolerance test in subjects with type 2 diabetes mellitus (DM) and reduces food intake in healthy human subjects. A reduction in food consumption and less weight gain occur in rats fed tagatose. This pilot study explored the metabolic effects of d-tag given daily to 8 human subjects with type 2 DM for 1 year. We hypothesized that this treatment period would lead to weight loss and improvements in glycated hemoglobin and the lipid profile. A 2-month run-in period was followed by a 12-month treatment period when 15 g of oral d-tag was taken 3 times daily with food. No serious adverse effects were seen during the 12-month treatment period. Ten of the initially 12 recruited subjects experienced gastrointestinal side effects that tended to be mild and transient. When 3 subjects were excluded who had oral diabetes, medications added and/or dosages increased during the study and mean (SD) body weight declined from 108.4 (9.0) to 103.3 (7.3) kg (P = .001). Glycated hemoglobin fell nonsignificantly from 10.6% ± 1.9% to 9.6% ± 2.3% (P = .08). High-density lipoprotein cholesterol progressively rose from a baseline level of 30.5 ± 15.8 to 41.7 ± 12.1 mg/dL at month 12 in the 6 subjects who did not have lipid-modifying medications added during the study (P < .001). Significant improvements in body weight and high-density lipoprotein cholesterol in this pilot study suggest that d-tag may be a potentially useful adjunct in the management of patients with type 2 DM. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. The total cholesterol to high-density lipoprotein cholesterol as a predictor of poor outcomes in a Chinese population with acute ischaemic stroke.

    Science.gov (United States)

    Chen, Lifang; Xu, Jianing; Sun, Hao; Wu, Hao; Zhang, Jinsong

    2017-11-01

    High admission cholesterol has been associated with better outcome after acute ischaemic stroke (AIS), but a paradox not completely illustrated. The purpose of this study was to investigate the effect of the total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) on short-term survival after AIS. Consecutive patients admitted in 2013 and 2015 were enrolled in the present study. The logistic regression analysis was conducted to evaluate predictors of 3-month outcomes. The primary endpoint was death. Secondary endpoint was good (modified Rankin Scale score 0-2 or equal to prestrike modified Rankin Scale score) at 3 months. Of 871 patients enrolled in the final analysis, 94 (10.8%) individuals died during 3 months of observation. The serum TC and TC/HDL-C levels at admission were significantly associated with stroke outcomes at 3 months, and the HDL-C level was only correlated with the good outcomes at 3 months. Mortality risk was markedly decreased for patients with high TC/HDL-C ratio (odds ratio: 0.23, 95% confidence interval [CI]: 0.10-0.50 for Q4:Q1; P-trend <.001) after adjustment. The effect of TC/HDL-C ratio on the probability of good outcomes was still obvious (odds ratio: 2.18, 95% CI: 1.40-3.39 for Q4:Q1; P-trend=.029). According to the receiver operating characteristic analyses, the best discriminating factor was a TG/HDL-C ≥3.37 (area under the ROC curve [AUC]=0.643, sensitivity 61.3%, specificity 61.7%) as well as the TC/HDL-C ≥4.09 for good outcomes (AUC: 0.587, sensitivity 63.9%, specificity 79.7%). High TC/HDL-C ratio may be associated with increased short-term survival and better outcomes after AIS. © 2017 Wiley Periodicals, Inc.

  2. Circulating Oxidized Low-Density Lipoprotein Levels Independently Predict 10-Year Progression of Subclinical Carotid Atherosclerosis: A Community-Based Cohort Study.

    Science.gov (United States)

    Gao, Shen; Zhao, Dong; Qi, Yue; Wang, Wei; Wang, Miao; Sun, Jiayi; Liu, Jun; Li, Yan; Liu, Jing

    2018-03-07

    To investigate the association between circulating oxidized low-density lipoprotein (ox-LDL) levels and progression of subclinical atherosclerosis and to examine whether this link is independent of other low-density lipoprotein (LDL)-related parameters. Totally, 804 subjects who were free of cardiovascular disease at baseline completed risk factor surveys and carotid ultrasound measurements in 2002 and 2012. Modified Poisson regression was performed to examine the association between baseline serum ox-LDL levels and the 10-year risk of progression of carotid atherosclerosis which was defined as the development of at least one new plaque in a previously plaque-free carotid segment at re-examination. The mean age of the subjects was 58.6±7.7 years at baseline and 43.3% were men. A total of 504 (62.7%) subjects had carotid plaque progression at re-examination. Subjects in the intermediate and highest tertiles of ox-LDL had a significantly higher adjusted risk of atherosclerosis progression than those in the lowest tertile [relative risk (95% confidence interval) 1.17 (1.01-1.34) for the intermediate tertile and 1.23 (1.07-1.42) for the highest tertile]. This association was independent of baseline levels of LDL-C, total LDL particle number, and small LDL particle number. This study demonstrates that serum ox-LDL levels predict 10-year progression of subclinical atherosclerosis. Moreover, this effect is independent of the cholesterol content, the number, and the size of LDL particles.

  3. Effect of methylglyoxal on the physico-chemical and biological properties of low-density lipoprotein

    NARCIS (Netherlands)

    Schalkwijk, C.G.; Vermeer, M.A.; Stehouwer, C.D.A.; Koppele, J. te; Princen, H.M.G.; Hinsbergh, V.W.M. van

    1998-01-01

    In patients with diabetes, non-enzymatic glycation of low-density lipoprotein (LDL) has been suggested to be involved in the development of atherosclerosis. α-Dicarbonyl compounds were identified as intermediates in the non-enzymatic glycation and increased levels were reported in patients with

  4. Waist-to-Height Ratio and Triglycerides/High-Density Lipoprotein Cholesterol Were the Optimal Predictors of Metabolic Syndrome in Uighur Men and Women in Xinjiang, China.

    Science.gov (United States)

    Chen, Bang-Dang; Yang, Yi-Ning; Ma, Yi-Tong; Pan, Shuo; He, Chun-Hui; Liu, Fen; Ma, Xiang; Fu, Zhen-Yan; Li, Xiao-Mei; Xie, Xiang; Zheng, Ying-Ying

    2015-06-01

    This study aimed to identify the best single predictor of metabolic syndrome by comparing the predictive ability of various anthropometric and atherogenic parameters among a Uighur population in Xinjiang, northwest China. A total of 4767 Uighur participants were selected from the Cardiovascular Risk Survey (CRS), which was carried out from October, 2007, to March, 2010. Anthropometric data, blood pressure, serum concentration of serum total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and fasting glucose were documented. Prevalence of metabolic syndrome and its individual components were confirmed according to International Diabetes Federation (IDF) criteria. Area under the receiver operating characteristic curve (AUC) of each variable for the presence of metabolic syndrome was compared. The sensitivity (Sen), specificity (Spe), distance in the receiver operating characteristic (ROC) curve, and cutoffs of each variable for the presence of metabolic syndrome were calculated. In all, 23.7% of men had the metabolic syndrome, whereas 40.1% of women had the metabolic syndrome in a Uighur population in Xinjiang; the prevalence of metabolic syndrome in women was significantly higher than that in men (PAUC value (AUC=0.838); it was followed by TGs/HDL-C (AUC=0.826), body mass index (BMI) (AUC=0.812), waist-to-hip ratio (WHR) (AUC=0.781), and body adiposity index (BAI) (AUC=0.709). In women, the TGs/HDL-C had the highest AUC value (AUC=0.815); it was followed by WHtR (AUC=0.780), WHR (AUC=0.730), BMI (AUC=0.719), and BAI (AUC=0.699). Similarly, among all five anthropometric and atherogenic parameters, the WHtR had the shortest ROC distance of 0.32 (Sen=85.40%, Spe=71.6%), and the optimal cutoff for WHtR was 0.55 in men. In women, TGs/HDL-C had the shortest ROC distance of 0.35 (Sen=75.29%, Spe=75.18%), and the optimal cutoff of TGs/HDL-C was 1.22. WHtR was the best predictor of metabolic

  5. Impact of high-density lipoprotein 3 cholesterol subfraction on periprocedural myocardial injury in patients who underwent elective percutaneous coronary intervention.

    Science.gov (United States)

    Harada, Kazuhiro; Kikuchi, Ryosuke; Suzuki, Susumu; Tanaka, Akihito; Aoki, Toshijiro; Iwakawa, Naoki; Kojima, Hiroki; Hirayama, Kenshi; Mitsuda, Takayuki; Sumi, Takuya; Negishi, Yosuke; Ishii, Hideki; Murohara, Toyoaki

    2018-02-02

    Periprocedural myocardial injury (PMI) is a major complication of percutaneous coronary intervention (PCI) and is associated with atherosclerotic coronary plaque and worse clinical outcomes. High-density lipoprotein cholesterol (HDL-C) is a protective factor for cardiovascular disease. However, the role of HDL-C subfractions, such as HDL2 cholesterol (HDL2-C) or HDL3 cholesterol (HDL3-C), in cardiovascular disease remains unclear. The purpose of the study was to investigate the relationship between HDL2-C and HDL3-C subfractions and the incidence of PMI in patients who underwent elective PCI. We enrolled 129 patients who underwent elective PCI for stable angina pectoris. PMI was defined as an increase in high-sensitivity troponin T levels > 5 times the upper normal limit (> 0.070 ng/mL) at 24 h after PCI. Serum HDL-C subfractions (HDL2-C and HDL3-C) were assessed using ultracentrifugation in patients with and those without PMI. HDL3-C levels were significantly lower in patients with PMI than in those without (15.1 ± 3.0 mg/dL vs. 16.4 ± 2.9 mg/dL, p = 0.016) and had an independent and inverse association with PMI (odds ratio, 0.86; 95% confidence interval, 0.74-0.99; p = 0.038). When divided by the cut-off value of HDL3-C for PMI (14.3 mg/dL), the incidence of PMI was significantly higher in low HDL3-C patients than in high HDL3-C patients (51.2% vs. 30.2%, p = 0.020). HDL3-C was an independent inverse predictor of PMI in patients who underwent elective PCI.

  6. Inhibitory Effects of North American Wild Rice on Monocyte Adhesion and Inflammatory Modulators in Low-Density Lipoprotein Receptor-Knockout Mice.

    Science.gov (United States)

    Moghadasian, Mohammed H; Zhao, Ruozhi; Ghazawwi, Nora; Le, Khuong; Apea-Bah, Franklin B; Beta, Trust; Shen, Garry X

    2017-10-18

    The present study examined the effects of wild rice on monocyte adhesion, inflammatory and fibrinolytic mediators in low-density lipoprotein receptor-knockout (LDLr-KO) mice. Male LDLr-KO mice received a cholesterol (0.06%, w/w)-supplemented diet with or without white or wild rice (60%, w/w) for 20 weeks. White rice significantly increased monocyte adhesion and abundances of monocyte chemoattractant protein-1, tissue necrosis factor-α, intracellular cell adhesion molecule-1, plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), and uPA receptor in aortae and hearts of LDLr-KO mice compared to the control diet. Wild rice inhibited monocyte adhesion to the aorta, atherosclerosis, and abundances of the inflammatory and fibrinolytic regulators in the cardiovascular tissue of LDLr-KO mice compared to white rice. White or wild rice did not significantly alter the levels of cholesterol, triglycerides, or antioxidant enzymes in plasma. The anti-atherosclerotic effect of wild rice may result from its inhibition on monocyte adhesion and inflammatory modulators in LDLr-KO mice.

  7. High density lipoproteins as indicators of endothelial dysfunction in children with diadetes type I

    Directory of Open Access Journals (Sweden)

    Lobanova S.M.

    2011-12-01

    Full Text Available The aim of the investigation was to study the level of blood high density lipoproteins (HDL in the groups of children with different course of diadetes type I in order to find out the dependence of course and complications of diabetes on that level. Materials and methods: Blood high density lipoprotein (HDL levels were investigated in children and adolescents with diadetes type I, depending on the duration of diadetes type I, age, stage of sexual development, the stage of diabetic nephropathy and levels of plasma endothelin-1 (E-1. Results: Decrease in HDL level with increasing duration of diadetes type I in prepubertate patients, higher indices of HDL cholesterol were determined in girls, especially with impaired puberty. HDL cholesterol was higher in diabetic nephropathy at the stage of proteinuria and high level of blood endothelin-1. Conclusion: The revealed changes were considered to cause deregulation of vascular endothelium as a manifestation of the initial stages of endothelial dysfunction

  8. Geometrical separation method for lipoproteins using bioformulated-fiber matrix electrophoresis: size of high-density lipoprotein does not reflect its density.

    Science.gov (United States)

    Tabuchi, Mari; Seo, Makoto; Inoue, Takayuki; Ikeda, Takeshi; Kogure, Akinori; Inoue, Ikuo; Katayama, Shigehiro; Matsunaga, Toshiyuki; Hara, Akira; Komoda, Tsugikazu

    2011-02-01

    The increasing number of patients with metabolic syndrome is a critical global problem. In this study, we describe a novel geometrical electrophoretic separation method using a bioformulated-fiber matrix to analyze high-density lipoprotein (HDL) particles. HDL particles are generally considered to be a beneficial component of the cholesterol fraction. Conventional electrophoresis is widely used but is not necessarily suitable for analyzing HDL particles. Furthermore, a higher HDL density is generally believed to correlate with a smaller particle size. Here, we use a novel geometrical separation technique incorporating recently developed nanotechnology (Nata de Coco) to contradict this belief. A dyslipidemia patient given a 1-month treatment of fenofibrate showed an inverse relationship between HDL density and size. Direct microscopic observation and morphological observation of fractionated HDL particles confirmed a lack of relationship between particle density and size. This new technique may improve diagnostic accuracy and medical treatment for lipid related diseases.

  9. Genetics of Lipid and Lipoprotein Disorders and Traits.

    Science.gov (United States)

    Dron, Jacqueline S; Hegele, Robert A

    2016-01-01

    Plasma lipids, namely cholesterol and triglyceride, and lipoproteins, such as low-density lipoprotein (LDL) and high-density lipoprotein, serve numerous physiological roles. Perturbed levels of these traits underlie monogenic dyslipidemias, a diverse group of multisystem disorders. We are on the verge of having a relatively complete picture of the human dyslipidemias and their components. Recent advances in genetics of plasma lipids and lipoproteins include the following: (1) expanding the range of genes causing monogenic dyslipidemias, particularly elevated LDL cholesterol; (2) appreciating the role of polygenic effects in such traits as familial hypercholesterolemia and combined hyperlipidemia; (3) accumulating a list of common variants that determine plasma lipids and lipoproteins; (4) applying exome sequencing to identify collections of rare variants determining plasma lipids and lipoproteins that via Mendelian randomization have also implicated gene products such as NPC1L1 , APOC3 , LDLR , APOA5 , and ANGPTL4 as causal for atherosclerotic cardiovascular disease; and (5) using naturally occurring genetic variation to identify new drug targets, including inhibitors of apolipoprotein (apo) C-III, apo(a), ANGPTL3, and ANGPTL4. Here, we compile this disparate range of data linking human genetic variation to plasma lipids and lipoproteins, providing a "one stop shop" for the interested reader.

  10. Association of Air Pollution Exposures With High-Density Lipoprotein Cholesterol and Particle Number: The Multi-Ethnic Study of Atherosclerosis.

    Science.gov (United States)

    Bell, Griffith; Mora, Samia; Greenland, Philip; Tsai, Michael; Gill, Ed; Kaufman, Joel D

    2017-05-01

    The relationship between air pollution and cardiovascular disease may be explained by changes in high-density lipoprotein (HDL). We examined the cross-sectional relationship between air pollution and both HDL cholesterol and HDL particle number in the MESA Air study (Multi-Ethnic Study of Atherosclerosis Air Pollution). Study participants were 6654 white, black, Hispanic, and Chinese men and women aged 45 to 84 years. We estimated individual residential ambient fine particulate pollution exposure (PM 2.5 ) and black carbon concentrations using a fine-scale likelihood-based spatiotemporal model and cohort-specific monitoring. Exposure periods were averaged to 12 months, 3 months, and 2 weeks prior to examination. HDL cholesterol and HDL particle number were measured in the year 2000 using the cholesterol oxidase method and nuclear magnetic resonance spectroscopy, respectively. We used multivariable linear regression to examine the relationship between air pollution exposure and HDL measures. A 0.7×10 - 6 m - 1 higher exposure to black carbon (a marker of traffic-related pollution) averaged over a 1-year period was significantly associated with a lower HDL cholesterol (-1.68 mg/dL; 95% confidence interval, -2.86 to -0.50) and approached significance with HDL particle number (-0.55 mg/dL; 95% confidence interval, -1.13 to 0.03). In the 3-month averaging time period, a 5 μg/m 3 higher PM 2.5 was associated with lower HDL particle number (-0.64 μmol/L; 95% confidence interval, -1.01 to -0.26), but not HDL cholesterol (-0.05 mg/dL; 95% confidence interval, -0.82 to 0.71). These data are consistent with the hypothesis that exposure to air pollution is adversely associated with measures of HDL. © 2017 American Heart Association, Inc.

  11. 21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

    Energy Technology Data Exchange (ETDEWEB)

    Gaibelet, Gérald [INSERM U563, CHU Purpan, Toulouse (France); CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette (France); Tercé, François [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Bertrand-Michel, Justine [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Lipidomic Platform Metatoul, Toulouse (France); Allart, Sophie [Plateau Technique d’Imagerie Cellulaire, INSERM U1043, Toulouse (France); Azalbert, Vincent [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Lecompte, Marie-France [INSERM U563, Faculté de Médecine de Rangueil, Toulouse (France); Collet, Xavier [Université Toulouse III, UMR 1048, Toulouse (France); INSERM U1048, Toulouse (France); Orlowski, Stéphane, E-mail: stephane.orlowski@cea.fr [INSERM U563, CHU Purpan, Toulouse (France); CEA, SB2SM and UMR8221 CNRS, IBiTec-Saclay, Gif-sur-Yvette (France)

    2013-11-01

    Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD

  12. 21-Methylpyrenyl-cholesterol stably and specifically associates with lipoprotein peripheral hemi-membrane: A new labelling tool

    International Nuclear Information System (INIS)

    Gaibelet, Gérald; Tercé, François; Bertrand-Michel, Justine; Allart, Sophie; Azalbert, Vincent; Lecompte, Marie-France; Collet, Xavier; Orlowski, Stéphane

    2013-01-01

    Highlights: •21-Methylpyrenyl-cholesterol specifically and stably associates to lipoproteins. •It is not esterified by LCAT, and thus reliably labels their peripheral hemi-membrane. •HDL vs. LDL are well distinguishable by various fluorescent labelling characteristics. •LDL peripheral hemi-membrane harbors cholesterol-rich ordered lipid (micro)domains. •Cultured cells can be stained by such labelled lipoproteins-mediated delivery. -- Abstract: Lipoproteins are important biological components. However, they have few convenient fluorescent labelling probes currently reported, and their physiological reliability can be questioned. We compared the association of two fluorescent cholesterol derivatives, 22-nitrobenzoxadiazole-cholesterol (NBD-Chol) and 21-methylpyrenyl-cholesterol (Pyr-met-Chol), to serum lipoproteins and to purified HDL and LDL. Both lipoproteins could be stably labelled by Pyr-met-Chol, but virtually not by NBD-Chol. At variance with NBD-Chol, LCAT did not esterify Pyr-met-Chol. The labelling characteristics of lipoproteins by Pyr-met-Chol were well distinguishable between HDL and LDL, regarding dializability, associated probe amount and labelling kinetics. We took benefit of the pyrene labelling to approach the structural organization of LDL peripheral hemi-membrane, since Pyr-met-Chol-labelled LDL, but not HDL, presented a fluorescence emission of pyrene excimers, indicating that the probe was present in an ordered lipid micro-environment. Since the peripheral membrane of LDL contains more sphingomyelin (SM) than HDL, this excimer formation was consistent with the existence of cholesterol- and SM-enriched lipid microdomains in LDL, as already suggested in model membranes of similar composition and reminiscent to the well-described “lipid rafts” in bilayer membranes. Finally, we showed that Pyr-met-Chol could stain cultured PC-3 cells via lipoprotein-mediated delivery, with a staining pattern well different to that observed with NBD

  13. Lipoprotein-associated phospholipase A2 distribution among lipoproteins differs in type 1 diabetes.

    Science.gov (United States)

    Jarvie, Jennifer L; Wang, Hong; Kinney, Gregory L; Snell-Bergeon, Janet; Hokanson, John E; Eckel, Robert H

    2016-01-01

    LpPLA2 mass and activity have been variably related to cardiovascular disease risk, and the distribution of LpPLA2 in patients with type 1 diabetes (T1D), wherein cardiovascular disease risk is high despite normal or higher levels of high-density lipoprotein (HDL) cholesterol, is unknown. To determine whether there are differences in the distribution of LpPLA2 mass and activity across lipoproteins and their association with coronary artery calcium (CAC) in patients with T1D. Men with T1D (n = 19) not on statins, with and without CAC progression, and men without diabetes matched for HDL cholesterol (n = 25) had lipoproteins separated by fast protein liquid chromatography. Both LpPLA2 mass and activity were found within low-density lipoprotein (LDL) and HDL pools with more LpPLA2 mass being associated with HDL (54% vs 44%; P-value lipoprotein subfractions was observed between all groups, and there was no relationship between LpPLA2 activity or mass and its distribution and CAC score progression in healthy or T1D men. LpPLA2 is found in both LDL and HDL and is distributed differently in men with T1D without any relationship to CAC score progression. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  14. The effect of ingestion of egg and low density lipoprotein (LDL oxidation on serum lipid profiles in hypercholesterolemic women

    Directory of Open Access Journals (Sweden)

    Taweesak Techakriengkrai1

    2012-04-01

    Full Text Available Egg is a major source of dietary cholesterol. The serum lipid response to egg shows marked individual variation, beingpartly genetically determined, and influence by ethnic groups and the overall diet response. In the present investigation, weinvestigated the effect of ingestion of egg and low density lipoprotein (LDL oxidation on serum lipid profile in hypercholesterolemicwomen. Forty hypercholesterolemic women volunteers on a cholesterol-lowering diet (CLD divided into 2 groups ina randomized controlled cross-over study of one egg per day (CLD + 1 egg for 4-week and three eggs per day (CLD + 3 eggsfor 4-week, separated by 4-week period egg-free. The body weight, blood pressure, serum lipid profiles and LDL oxidationwere measured at 4-week intervals. Cholesterol-lowering diet was applied throughout the study by a dietitian using a foodexchange program and 3-day dietary recall every 4 weeks. Compared to the values obtained at baseline, the mean serum totalcholesterol and LDL cholesterol of CLD + 3 eggs was not significantly different from baseline whereas of those of 4-week ofegg-free period and CLD + 1 egg were significantly decreased (238.3±2.9 mg/dL and 228.3±4.7 mg/dL compared to thebaseline (252.2±5.9 mg/dL as was LDL cholesterol (161.2±3.0 mg/dL and 155.7±4.8 mg/dL compared to the baseline (177.5±6.0 mg/dL (p<0.05. The study showed there were no significantly difference the body weight, blood pressure, HDL cholesterol,triglycerides or LDL oxidation during the study. However, serum total cholesterol and LDL cholesterol of 1 or 3 eggsper day after 4-week of egg consumption was not significantly higher than the egg-free period. The study suggests that inhypercholesterolemic women who are on cholesterol-lowering diet, consuming one or three eggs per day did not raise serumcholesterol or LDL cholesterol levels at 4 weeks or result in any change in LDL oxidation.

  15. Terminalia pallida fruit ethanolic extract ameliorates lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase in isoproterenol-induced myocardial infarcted rats

    Directory of Open Access Journals (Sweden)

    Althaf Hussain Shaik

    2018-03-01

    Full Text Available The present study aimed to evaluate the effect of Terminalia pallida fruit ethanolic extract (TpFE on lipids, lipoproteins, lipid metabolism marker enzymes and paraoxonase (PON in isoproterenol (ISO-induced myocardial infarcted rats. PON is an excellent serum antioxidant enzyme which involves in the protection of low density lipoprotein cholesterol (LDL-C from the process of oxidation for the prevention of cardiovascular diseases. ISO caused a significant increase in the concentration of total cholesterol, triglycerides, LDL-C, very low density lipoprotein cholesterol and lipid peroxidation whereas significant decrease in the concentration of high density lipoprotein cholesterol. ISO administration also significantly decreased the activities of lecithin cholesterol acyl transferase, PON and lipoprotein lipase whereas significantly increased the activity of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase. Oral pretreatment of TpFE at doses 100, 300 and 500 mg/kg body weight (bw and gallic acid (15 mg/kg bw for 30 days challenged with concurrent injection of ISO (85 mg/kg bw on 29th and 30th day significantly attenuated these alterations and restored the levels of lipids, lipoproteins and the activities of lipid metabolizing enzymes. Also TpFE significantly elevated the serum antioxidant enzyme PON. This is the first report revealed that pretreatment with TPFE ameliorated lipid metabolic marker enzymes and increased the antioxidant PON in ISO treated male albino Wistar rats. Keywords: Terminalia pallida fruit, Gallic acid, Isoproterenol, Lipid metabolism marker enzymes, Paraoxonase, Myocardial infarction

  16. Maternal plasma cholesterol and duration of pregnancy: A prospective cohort study in Ghana.

    Science.gov (United States)

    Oaks, Brietta M; Stewart, Christine P; Laugero, Kevin D; Adu-Afarwuah, Seth; Lartey, Anna; Vosti, Stephen A; Ashorn, Per; Dewey, Kathryn G

    2017-10-01

    Low plasma cholesterol may be associated with preterm birth; however, results are mixed and limited primarily to high-income countries. Our objective was to determine whether maternal plasma lipid concentrations are associated with pregnancy duration. We performed a nested cohort (n = 320) study of pregnant Ghanaian women enrolled in a randomized controlled trial. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglyceride concentrations were analyzed in plasma at ≤20and 36 weeks gestation as continuous variables and also categorized into low, referent, or high (90th percentile). At ≤20 weeks, plasma lipid concentrations were not associated with pregnancy duration. At 36 weeks, total cholesterol and triglyceride concentrations were not associated with pregnancy duration. Higher HDL-C at 36 weeks was associated with a longer pregnancy duration (adjusted β-coefficient ± standard error: 0.05 ± 0.02 days mg -1 /dL, p = .02); pregnancy duration was 5.9 ± 2.0 (mean ± standard error) days shorter among women with low HDL-C compared with the referent group (10th-90th percentile) (p = .02) and 8.6 ± 2.6 days shorter when compared with the high HDL-C group (p = .003). Pregnancy duration was 4.9 ± 2.1 days longer among women with low low-density lipoprotein cholesterol at 36 weeks gestation when compared with the referent group (p = .051). Our data suggest that low HDL-C in the third trimester of pregnancy is associated with a shorter duration of pregnancy in this study population but do not support the hypothesis that low total cholesterol is associated with a shorter pregnancy duration. © 2016 John Wiley & Sons Ltd.

  17. The multiligand α2-macroglobulin receptor/low density lipoprotein receptor-related protein

    DEFF Research Database (Denmark)

    Gliemann, Jørgen; Nykjær, Anders; Petersen, Claus Munck

    1994-01-01

    The fusion of separate lines of research has greatly helped in elucidating the function of the giant members of the low density lipoprotein (LDL) receptor (LDLR) supergene family. The cDNA encoding a large protein structurally closely related to LDLR, and hence named LDLR-related protein (LRP......), was cloned by Herz et al. in 1988.'Evidence was provided demonstrating that LRP can function as a receptor for chylomicron remnants@-migrating very low density lipoproteins (P-VLDL) rich in apolipoprotein E (apoE)?' The a2-macroglobulin (a2M) receptor (a2MR) was purified from rat livep and human p l a~e n t...... from the observation that affinity-purified a2MR/LRP contains a 40-kDa5.8 or 39-kDa6.' protein, designated a2MRAP, in addition to the a2MFULRP a- and P-chains. cDNA cloning" disclosed the 323-residue protein as both the human homologue of mouse heparin binding protein 44 (see reference 11) and...

  18. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Directory of Open Access Journals (Sweden)

    Mafu Akier

    2002-01-01

    Full Text Available Abstract Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent.

  19. Langmuir-Blodgett films of polyaniline for low density lipoprotein detection

    Energy Technology Data Exchange (ETDEWEB)

    Matharu, Zimple [Department of Science and Technology Centre on Biomolecular Electronics, Biomedical Instrumentation Section, National Physical Laboratory (CSIR), Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Department of Physics and Astrophysics, University of Delhi, Delhi-110007 (India); Sumana, G. [Department of Science and Technology Centre on Biomolecular Electronics, Biomedical Instrumentation Section, National Physical Laboratory (CSIR), Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Gupta, Vinay [Department of Physics and Astrophysics, University of Delhi, Delhi-110007 (India); Malhotra, B.D., E-mail: bansi.malhotra@gmail.co [Department of Science and Technology Centre on Biomolecular Electronics, Biomedical Instrumentation Section, National Physical Laboratory (CSIR), Dr. K. S. Krishnan Marg, New Delhi-110012 (India)

    2010-11-30

    Langmuir-Blodgett (LB) films of polyaniline (PANI) were utilized for the fabrication of impedimetric immunosensor for detection of human plasma low density lipoprotein (LDL) by immobilizing anti-apolipoprotein B (AAB) via EDC-NHS coupling. The modified electrodes were characterized by electrochemical impedance spectroscopy (EIS) and scanning electron microscopy. AAB/PANI-SA LB immunoelectrodes studied by EIS spectroscopy revealed detection of LDL in the wide range of 0.018 {mu}M (6 mg/dl) to 0.39 {mu}M (130 mg/dl), covering the physiological range in blood, with a sensitivity of 11.25 k{Omega} {mu}M{sup -1}.

  20. Langmuir-Blodgett films of polyaniline for low density lipoprotein detection

    International Nuclear Information System (INIS)

    Matharu, Zimple; Sumana, G.; Gupta, Vinay; Malhotra, B.D.

    2010-01-01

    Langmuir-Blodgett (LB) films of polyaniline (PANI) were utilized for the fabrication of impedimetric immunosensor for detection of human plasma low density lipoprotein (LDL) by immobilizing anti-apolipoprotein B (AAB) via EDC-NHS coupling. The modified electrodes were characterized by electrochemical impedance spectroscopy (EIS) and scanning electron microscopy. AAB/PANI-SA LB immunoelectrodes studied by EIS spectroscopy revealed detection of LDL in the wide range of 0.018 μM (6 mg/dl) to 0.39 μM (130 mg/dl), covering the physiological range in blood, with a sensitivity of 11.25 kΩ μM -1 .

  1. Non-high-density lipoprotein cholesterol calculation and goal awareness among physicians-in-training.

    Science.gov (United States)

    Negi, Smita I; Steinberg, Lynne; Polsani, Venkateshwar R; Gowani, Saqib A; Nambi, Vijay; Kumar, Varinder; Marinescu, Victor; Jones, Peter H; Petersen, Laura A; Ballantyne, Christie M; Virani, Salim S

    2012-01-01

    Non-high density lipoprotein cholesterol (non-HDL-C) goal attainment per Adult Treatment Panel III (ATP III) guidelines remains low. To understand gaps in knowledge and practices of physicians-in-training (internal medicine, family medicine, cardiology, endocrinology) towards non-HDL-C. A survey based on a conceptual model to assess the trainee's knowledge, attitudes, and practice regarding non-HDL-C was developed and administered to physicians-in-training (n = 655) at 26 training programs in the United States. Responses of those in internal medicine and family medicine (residents-in-training; n = 418) were compared with those in cardiology and endocrinology (fellows-in-training; n = 124). Response rate was 83.7%. Fifty-three percent of residents and 31% of fellows-in-training had not read the ATP III guidelines (P training could not calculate non-HDL-C from a standard lipid panel (P = .7). Sixty-seven percent of the residents and 52% of fellows were not aware of treatment goals for non-HDL-C (P = .004 for comparison between residents and fellows). Both residents and fellows reported infrequent calculation of non-HDL-C levels in patients with elevated triglycerides (≥200 mg/dL; 32.5% vs 35.4%, respectively, P = .6). Lack of familiarity with ATP III guidelines, lack of knowledge regarding importance of non-HDL-C, lack of institutional mandate to calculate non-HDL-C, and lack of emphasis on non-HDL-C by teaching staff were reported as barriers to non-HDL-C use in routine clinical practice. At least one-third of physicians-in-training could not calculate non-HDL-C from a standard lipid panel, and a large number were not aware of ATP III treatment goals pertaining to non-HDL-C. This area represents one for improvement if non-HDL-C is to be retained as a treatment target in the forthcoming ATP-IV guidelines. Published by Elsevier Inc.

  2. Effect of Porphyromonas gingivalis infection on post-transcriptional regulation of the low-density lipoprotein receptor in mice

    Directory of Open Access Journals (Sweden)

    Miyazawa Haruna

    2012-09-01

    Full Text Available Abstract Background Periodontal disease is suggested to increase the risk of atherothrombotic disease by inducing dyslipidemia. Recently, we demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9, which is known to play a critical role in the regulation of circulating low-density lipoprotein (LDL cholesterol levels, is elevated in periodontitis patients. However, the underlying mechanisms of elevation of PCSK9 in periodontitis patients are largely unknown. Here, we explored whether Porphyromonas gingivalis, a representative periodontopathic bacterium, -induced inflammatory response regulates serum PCSK9 and cholesterol levels using animal models. Methods We infected C57BL/6 mice intraperitoneally with Porphyromonas gingivalis, a representative strain of periodontopathic bacteria, and evaluated serum PCSK9 levels and the serum lipid profile. PCSK9 and LDL receptor (LDLR gene and protein expression, as well as liver X receptors (Lxrs, inducible degrader of the LDLR (Idol, and sterol regulatory element binding transcription factor (Srebf2 gene expression, were examined in the liver. Results P. gingivalis infection induced a significant elevation of serum PCSK9 levels and a concomitant elevation of total and LDL cholesterol compared with sham-infected mice. The LDL cholesterol levels were significantly correlated with PCSK9 levels. Expression of the Pcsk9, Ldlr, and Srebf2 genes was upregulated in the livers of the P. gingivalis-infected mice compared with the sham-infected mice. Although Pcsk9 gene expression is known to be positively regulated by sterol regulatory element binding protein (SREBP2 (human homologue of Srebf2, whereas Srebf2 is negatively regulated by cholesterol, the elevated expression of Srebf2 found in the infected mice is thought to be mediated by P. gingivalis infection. Conclusions P. gingivalis infection upregulates PCSK9 production via upregulation of Srebf2, independent of cholesterol levels. Further studies

  3. Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome.

    Science.gov (United States)

    Song, Do Kyeong; Lee, Hyejin; Sung, Yeon Ah; Oh, Jee Young

    2016-11-01

    The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG.

  4. Testosterone is an independent determinant of bone mineral density in men with type 2 diabetes mellitus.

    Science.gov (United States)

    Vasilkova, Olga; Mokhort, Tatiana; Sanec, Igor; Sharshakova, Tamara; Hayashida, Naomi; Takamura, Noboru

    2011-01-01

    Although many reports have elucidated pathophysiological characteristics of abnormal bone metabolism in patients with type 2 diabetes mellitus (DT2), determinants of bone mineral density (BMD) in patients with DT2 are still controversial. We examined 168 Belarussian men 45-60 years of age. Plasma total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, triglycerides, hemoglobin A(1c) (HbA(1c)), immunoreactive insulin, and C-reactive protein concentrations were assessed. BMD was measured using dual energy X-ray densitometry of the lumbar spine (L(1)-L(4)). Total testosterone (TT) and sex hormone-binding globulin were measured, and free testosterone (FT) was calculated. Using univariate linear regression analysis, BMD of the lumbar spine was significantly correlated with FT (r=0.32, pDT2.

  5. Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Freiberg, Jacob J

    2011-01-01

    Non-fasting triglycerides are measured at any time within up to 8 h (14 h) after any normal meal, while postprandial triglycerides are measured at a fixed time point within up to 8 h (14 h) of a standardised fat tolerance test. The simplest possible way of evaluating remnant cholesterol is non......-fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non......-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0...

  6. Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD

    Directory of Open Access Journals (Sweden)

    Funamoto M

    2016-08-01

    Full Text Available Masafumi Funamoto,1,2 Yoichi Sunagawa,1–3 Yasufumi Katanasaka,1–3 Yusuke Miyazaki,1,2 Atsushi Imaizumi,4 Hideaki Kakeya,5 Hajime Yamakage,2 Noriko Satoh-Asahara,2 Maki Komiyama,2 Hiromichi Wada,2 Koji Hasegawa,2 Tatsuya Morimoto1–3 1Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2Clinical Research Institute, National Hospital Organization Kyoto Medical Center, Kyoto, 3Shizuoka General Hospital, Shizuoka, 4Theravalues Corporation, Kioicho, Tokyo, 5Department of System Chemotherapy and Molecular Sciences, Division of Bioinformatics and Chemical Genomics, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan Purpose: COPD is mainly caused by tobacco smoking and is associated with a high frequency of coronary artery disease. There is growing recognition that the inflammation in COPD is not only confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs, including blood vessels. α1-antitrypsin–low-density lipoprotein (AT-LDL complex is an oxidatively modified LDL that accelerates atherosclerosis. Curcumin, one of the best-investigated natural products, is a powerful antioxidant. However, the effects of curcumin on AT-LDL remain unknown. We hypothesized that Theracurmin®, a highly absorptive curcumin with improved bioavailability using a drug delivery system, ameliorates the inflammatory status in subjects with mild COPD.Patients and methods: This is a randomized, double-blind, parallel-group study. Subjects with stages I–II COPD according to the Japanese Respiratory Society criteria were randomly assigned to receive 90 mg Theracurmin® or placebo twice a day for 24 weeks, and changes in inflammatory parameters were evaluated.Results: There were no differences between the Theracurmin® and placebo groups in terms of age, male/female ratio, or body mass index in 39 evaluable subjects. The percent changes in blood pressure

  7. The Success Story of LDL Cholesterol Lowering.

    Science.gov (United States)

    Pedersen, Terje R

    2016-02-19

    We can look back at >100 years of cholesterol research that has brought medicine to a stage where people at risk of severe or fatal coronary heart disease have a much better prognosis than before. This progress has not come about without resistance. Perhaps one of the most debated topics in medicine, the cholesterol controversy, could only be brought to rest through the development of new clinical research methods that were capable of taking advantage of the amazing achievements in basic and pharmacological science after the second World War. It was only after understanding the biochemistry and physiology of cholesterol synthesis, transport and clearance from the blood that medicine could take advantage of drugs and diets to reduce the risk of atherosclerotic diseases. This review points to the highlights of the history of low-density lipoprotein-cholesterol lowering, with the discovery of the low-density lipoprotein receptor and its physiology and not only the development of statins as the stellar moments but also the development of clinical trial methodology as an effective tool to provide scientifically convincing evidence. © 2016 American Heart Association, Inc.

  8. Oxidized low-density lipoproteins upregulate proline oxidase to initiate ROS-dependent autophagy

    OpenAIRE

    Zabirnyk, Olga; Liu, Wei; Khalil, Shadi; Sharma, Anit; Phang, James M.

    2009-01-01

    Epidemiological studies showed that high levels of oxidized low-density lipoproteins (oxLDLs) are associated with increased cancer risk. We examined the direct effect of physiologic concentrations oxLDL on cancer cells. OxLDLs were cytotoxic and activate both apoptosis and autophagy. OxLDLs have ligands for peroxisome proliferator-activated receptor gamma and upregulated proline oxidase (POX) through this nuclear receptor. We identified 7-ketocholesterol (7KC) as a main component responsible ...

  9. Plasma lecithin : cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

    NARCIS (Netherlands)

    Dullaart, R. P. F.; Perton, F.; Kappelle, P.J.W.H.; de Vries, R.; Sluiter, W. J.; van Tol, A.

    Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL We determined the relationship of plasma high-sensitivity

  10. Polygenic determinants in extremes of high-density lipoprotein cholesterol[S

    Science.gov (United States)

    Dron, Jacqueline S.; Wang, Jian; Low-Kam, Cécile; Khetarpal, Sumeet A.; Robinson, John F.; McIntyre, Adam D.; Ban, Matthew R.; Cao, Henian; Rhainds, David; Dubé, Marie-Pierre; Rader, Daniel J.; Lettre, Guillaume; Tardif, Jean-Claude

    2017-01-01

    HDL cholesterol (HDL-C) remains a superior biochemical predictor of CVD risk, but its genetic basis is incompletely defined. In patients with extreme HDL-C concentrations, we concurrently evaluated the contributions of multiple large- and small-effect genetic variants. In a discovery cohort of 255 unrelated lipid clinic patients with extreme HDL-C levels, we used a targeted next-generation sequencing panel to evaluate rare variants in known HDL metabolism genes, simultaneously with common variants bundled into a polygenic trait score. Two additional cohorts were used for validation and included 1,746 individuals from the Montréal Heart Institute Biobank and 1,048 individuals from the University of Pennsylvania. Findings were consistent between cohorts: we found rare heterozygous large-effect variants in 18.7% and 10.9% of low- and high-HDL-C patients, respectively. We also found common variant accumulation, indicated by extreme polygenic trait scores, in an additional 12.8% and 19.3% of overall cases of low- and high-HDL-C extremes, respectively. Thus, the genetic basis of extreme HDL-C concentrations encountered clinically is frequently polygenic, with contributions from both rare large-effect and common small-effect variants. Multiple types of genetic variants should be considered as contributing factors in patients with extreme dyslipidemia. PMID:28870971

  11. Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL)

    DEFF Research Database (Denmark)

    Ismael, Fahd O; Proudfoot, Julie M; Brown, Bronwyn E

    2015-01-01

    Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces ox...

  12. High-Density Lipoprotein Cholesterol, Blood Urea Nitrogen, and Serum Creatinine Can Predict Severe Acute Pancreatitis.

    Science.gov (United States)

    Hong, Wandong; Lin, Suhan; Zippi, Maddalena; Geng, Wujun; Stock, Simon; Zimmer, Vincent; Xu, Chunfang; Zhou, Mengtao

    2017-01-01

    Early prediction of disease severity of acute pancreatitis (AP) would be helpful for triaging patients to the appropriate level of care and intervention. The aim of the study was to develop a model able to predict Severe Acute Pancreatitis (SAP). A total of 647 patients with AP were enrolled. The demographic data, hematocrit, High-Density Lipoprotein Cholesterol (HDL-C) determinant at time of admission, Blood Urea Nitrogen (BUN), and serum creatinine (Scr) determinant at time of admission and 24 hrs after hospitalization were collected and analyzed statistically. Multivariate logistic regression indicated that HDL-C at admission and BUN and Scr at 24 hours (hrs) were independently associated with SAP. A logistic regression function (LR model) was developed to predict SAP as follows: -2.25-0.06 HDL-C (mg/dl) at admission + 0.06 BUN (mg/dl) at 24 hours + 0.66 Scr (mg/dl) at 24 hours. The optimism-corrected c-index for LR model was 0.832 after bootstrap validation. The area under the receiver operating characteristic curve for LR model for the prediction of SAP was 0.84. The LR model consists of HDL-C at admission and BUN and Scr at 24 hours, representing an additional tool to stratify patients at risk of SAP.

  13. Kinetics of incorporation/redistribution of photosensitizer hypericin to/from high-density lipoproteins.

    Science.gov (United States)

    Joniova, Jaroslava; Buriankova, Luboslava; Buzova, Diana; Miskovsky, Pavol; Jancura, Daniel

    2014-11-20

    By means of fluorescence spectroscopy we have studied the kinetics of interaction of a photosensitizer hypericin (Hyp) with high-density lipoproteins (HDL). Hyp is incorporated into HDL molecules as monomer till ratio Hyp/HDL ∼8:1 and above this ratio forms non-fluorescent aggregates. This number is different from that found in the case of Hyp incorporation into low-density lipoprotein (LDL) molecules (8:1 vs 30:1). The difference is mainly attributed to the smaller size of HDL in comparison with LDL molecule. Biphasic kinetics of Hyp association with HDL was observed. The rapid phase of incorporation is completed within seconds, while the slow one lasts several minutes. The kinetics of the association of Hyp molecules with free HDL, Hyp/HDL=10:1 complex and the redistribution of Hyp from Hyp/HDL=70:1 complex to free HDL molecules reveal a qualitative similar characteristics of these processes with those observed for the interaction of Hyp with LDL. However, the incorporation of Hyp into HDL in the "slow" phase is more rapid than to LDL and extend of Hyp penetration into lipoproteins in the fast phase is also much higher in the case of HDL. The lower concentration of cholesterol molecules in outer shell of HDL particles is probably the determining factor for the more rapid kinetics of Hyp incorporation to and redistribution from these molecules when comparing with LDL particles. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Comparing fluorescence-based cell-free assays for the assessment of antioxidative capacity of high-density lipoproteins

    Science.gov (United States)

    Background: Population studies have shown an inverse association between high-density lipoprotein (HDL) cholesterol levels and risk of coronary heart disease (CHD). HDL has different functions, including the ability to protect biological molecules from oxidation. Our aim was to evaluate the performa...

  15. Uptake of [3H]vitamin D3 from low and high density lipoproteins by cultured human fibroblasts

    International Nuclear Information System (INIS)

    Shireman, R.B.; Williams, D.; Remsen, J.F.

    1986-01-01

    The plasma distribution and cellular uptake of [ 3 H]vitamin D 3 was studied in vitro using cultured human fibroblasts. Incubation of [ 3 H]vitamin D 3 (cholecalciferol) with plasma followed by sequential ultracentrifugal fractionation of the lipoproteins indicated that 2-4% of the radioactivity associated with the very low density lipoprotein (VLDL), 12% with low density lipoprotein (LDL), and approximately 60% with the high density lipoprotein (HDL). The remaining radioactivity, 25%, was associated with the sedimented plasma fractions. By comparison, an average of 86% of the radioactivity from [ 3 H] 1,25-dihydroxycholecalciferol associated with the sedimented plasma fractions. The uptake of [ 3 H]vitamin D 3 from plasma, LDL, or HDL was studied in cultured human cells; uptake by normal fibroblasts was greatest from LDL and least from plasma. The cellular association of vitamin D 3 was time, concentration, and temperature dependent. At a concentration of 50 μg LDL/ml of medium, the uptake of [ 3 H]vitamin D 3 from LDL at 37 0 C was rapid and reached a maximum at approximately 4 hr; it was slower from HDL but continued to increase slowly up to 24 hr. The significance of these in vitro findings is uncertain since much of the vitamin D 3 absorbed from the intestine reportedly associates with chylomicrons and is rapidly taken up by the liver

  16. A Healthy Balance of Plasma Cholesterol by a Novel Annurca Apple-Based Nutraceutical Formulation: Results of a Randomized Trial

    OpenAIRE

    Tenore, Gian Carlo; Caruso, Domenico; Buonomo, Giuseppe; D'Avino, Maria; Campiglia, Pietro; Marinelli, Luciana; Novellino, Ettore

    2017-01-01

    Abstract Cardiovascular diseases are nowadays preferential targets of preventive medicine through a straightforward therapy on lipid profile. However, statins, the first-line lipid-lowering drug therapy, specifically act on low-density lipoprotein cholesterol (LDL-C), having a modest effect on plasma high-density lipoprotein cholesterol (HDL-C) concentrations. Today, a number of novel HDL-targeted therapies are emerging, along with unexpected side effects. Thus, novel and possibly safe substa...

  17. Low-Density Lipoproteins Oxidation and Endometriosis

    Directory of Open Access Journals (Sweden)

    Grzegorz Polak

    2013-01-01

    Full Text Available The etiopathogenesis of endometriosis still remains unknown. Recent data provide new valuable information concerning the role of oxidative stress in the pathophysiology of the disease. It has been proved that levels of different lipid peroxidation end products are increased in both peritoneal fluid (PF and serum of endometriotic patients. We assessed the concentration of oxidized low-density lipoproteins (oxLDL in PF of 110 women with different stages of endometriosis and 119 women with serous ( or dermoid ( ovarian cysts, as the reference groups. PF oxLDL levels were evaluated by ELISA. We found that concentrations of oxLDL in PF of endometriotic women were significantly higher compared to women with serous but not dermoid ovarian cysts. Interestingly, by analyzing concentrations of oxLDL in women with different stages of the disease, it was noted that they are significantly higher only in the subgroup of patients with stage IV endometriosis as compared to women with ovarian serous cysts. In case of minimal, mild, and moderate disease, PF oxLDL levels were similar to those noted in reference groups. Our results indicate that disrupted oxidative status in the peritoneal cavity of women with endometriosis may play a role in the pathogenesis of advanced stages of the disease.

  18. Remnant cholesterol as a causal risk factor for ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol.......The aim of this study was to test the hypothesis that elevated nonfasting remnant cholesterol is a causal risk factor for ischemic heart disease independent of reduced high-density lipoprotein (HDL) cholesterol....

  19. Effect of tomato consumption on high-density lipoprotein cholesterol level: a randomized, single-blinded, controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Cuevas-Ramos D

    2013-07-01

    Full Text Available Daniel Cuevas-Ramos,1 Paloma Almeda-Valdés,1 Emma Chávez-Manzanera,1 Clara Elena Meza-Arana,2 Griselda Brito-Córdova,1 Roopa Mehta,1 Oscar Pérez-Méndez,3 Francisco J Gómez-Pérez1 1Department of Endocrinology and Metabolism, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 2Department of Internal Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 3Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico Introduction: Epidemiologic evidence suggests that tomato-based products could reduce the risk of cardiovascular diseases. One of the main cardiovascular risk factors is low levels of high-density lipoprotein cholesterol (HDL-C. This study aimed to prospectively evaluate the effect of tomato consumption on HDL-C levels. Subject and methods: We conducted a randomized, single-blinded, controlled clinical trial. We screened 432 subjects with a complete lipid profile. Those individuals with low HDL-C (men 40 mg/dL. A linear regression model that adjusted for those parameters that impact HDL-C levels (age, gender, waist-to-hip ratio, body mass index, fasting triglyceride concentration, simple sugars, alcohol, physical activity, and omega-3 consumption showed an independent association between tomato consumption and the increase in HDL-C (r2 = 0.69; P > 0.0001. Conclusion: Raw tomato consumption produced a favorable effect on HDL-C levels in overweight women. Keywords: lycopene, hypoalphalipoproteinemia, dyslipidemia, overweight, cardiovascular diseases

  20. Evaluation of high density lipoprotein as a circulating biomarker of Gaucher disease activity

    Science.gov (United States)

    Stein, Philip; Yang, Ruhua; Liu, Jun; Pastores, Gregory M.; Mistry, Pramod K.

    2011-01-01

    Circulating biomarkers are important surrogates for monitoring disease activity in type I Gaucher disease (GD1). We and others have reported low high-density lipoprotein (HDL) in GD1. We assessed HDL cholesterol as a biomarker of GD1, with respect to its correlation with indicators of disease severity and its response to imiglucerase enzyme replacement therapy (ERT). In 278 consecutively evaluated GD1 patients, we correlated HDL cholesterol, chitotriosidase, and angiotensin-converting enzyme (ACE) with indicators of disease severity. Additionally, we measured the response of these biomarkers to ERT. HDL cholesterol was negatively correlated with spleen volume, liver volume, and GD severity score index; the magnitude of this association of disease severity with HDL cholesterol was similar to that for ACE and for chitotriosidase. Within individual patients monitored over many years, there was a strikingly strong correlation of HDL with liver and spleen volumes; there was a similarly strong correlation of chitotriosidase and ACE with disease severity in individual patients monitored serially over many years (chitotriosidase r=0.96 to 0.98, ACE r =0.88 to 0.94, and HDL r=−0.84 to −0.94, p<0.001). ERT for 3 years resulted in a striking increase of HDL while serum levels of chitotriosidase and ACE decreased. Our results reveal markedly low HDL cholesterol in untreated GD1, a correlation with indicators of disease severity in GD1, and a rise towards normal after ERT. These findings suggest HDL cholesterol merits inclusion within the “biomarker basket” for monitoring of patients with GD1. PMID:21290183

  1. The fibrate drug gemfibrozil disrupts lipoprotein metabolism in rainbow trout

    International Nuclear Information System (INIS)

    Prindiville, John S.; Mennigen, Jan A.; Zamora, Jake M.; Moon, Thomas W.; Weber, Jean-Michel

    2011-01-01

    Gemfibrozil (GEM) is a fibrate drug consistently found in effluents from sewage treatment plants. This study characterizes the pharmacological effects of GEM on the plasma lipoproteins of rainbow trout (Oncorhynchus mykiss). Our goals were to quantify the impact of the drug on: 1) lipid constituents of lipoproteins (phospholipids (PL), triacylglycerol (TAG), and cholesterol), 2) lipoprotein classes (high, low and very low density lipoproteins), and 3) fatty acid composition of lipoproteins. Potential mechanisms of GEM action were investigated by measuring lipoprotein lipase activity (LPL) and the hepatic gene expression of LPL and of the peroxisome proliferator-activated receptor (PPAR) α, β, and γ isoforms. GEM treatment resulted in decreased plasma lipoprotein levels (- 29%) and a reduced size of all lipoprotein classes (lower PL:TAG ratios). However, the increase in HDL-cholesterol elicited by GEM in humans failed to be observed in trout. Therefore, HDL-cholesterol cannot be used to assess the impact of the drug on fish. GEM also modified lipoprotein composition by reducing the abundance of long-chain n-3 fatty acids, thereby potentially reducing the nutritional quality of exposed fish. The relative gene expression of LPL was increased, but the activity of the enzyme was not, and we found no evidence for the activation of PPAR pathways. The depressing effects of GEM on fish lipoproteins demonstrated here may be a concern in view of the widespread presence of fibrates in aquatic environments. Work is needed to test whether exposure to environmental concentrations of these drugs jeopardizes the capacity of fish for reproduction, temperature acclimation or migratory behaviors.

  2. Properties of low-fat, low-cholesterol egg yolk prepared by supercritical CO2 extraction.

    Science.gov (United States)

    Bringe, N A

    1997-01-01

    A dry egg yolk ingredient called Eggcellent has 74% less fat and 90% less cholesterol than liquid egg yolks, when reconstituted on an equal protein basis. The phospholipids and proteins are retained, enabling the ingredient to have the taste and texturizing properties of fresh egg yolk. Using the new yolk, it is possible to significantly improve the acceptability of low-fat, low-cholesterol bakery products, scrambled eggs and mayonnaise dressings without losing nutritional claims. The structures and functional properties of egg yolk components and the conditions required to optimize their benefits in foods are reviewed. The lipoproteins of low-fat, low-cholesterol yolk have valuable properties as flavorants, texturizers, foaming agents, emulsifiers, antioxidants, colorants, and nutraceuticals.

  3. Fluid-Phase Pinocytosis of Native Low Density Lipoprotein Promotes Murine M-CSF Differentiated Macrophage Foam Cell Formation

    Science.gov (United States)

    Xu, Qing; Bohnacker, Thomas; Wymann, Matthias P.; Kruth, Howard S.

    2013-01-01

    During atherosclerosis, low-density lipoprotein (LDL)-derived cholesterol accumulates in macrophages to form foam cells. Macrophage uptake of LDL promotes foam cell formation but the mechanism mediating this process is not clear. The present study investigates the mechanism of LDL uptake for macrophage colony-stimulating factor (M-CSF)-differentiated murine bone marrow-derived macrophages. LDL receptor-null (LDLR−/−) macrophages incubated with LDL showed non-saturable accumulation of cholesterol that did not down-regulate for the 24 h examined. Incubation of LDLR−/− macrophages with increasing concentrations of 125I-LDL showed non-saturable macrophage LDL uptake. A 20-fold excess of unlabeled LDL had no effect on 125I-LDL uptake by wild-type macrophages and genetic deletion of the macrophage scavenger receptors CD36 and SRA did not affect 125I-LDL uptake, showing that LDL uptake occurred by fluid-phase pinocytosis independently of receptors. Cholesterol accumulation was inhibited approximately 50% in wild-type and LDLR−/− mice treated with LY294002 or wortmannin, inhibitors of all classes of phosphoinositide 3-kinases (PI3K). Time-lapse, phase-contrast microscopy showed that macropinocytosis, an important fluid-phase uptake pathway in macrophages, was blocked almost completely by PI3K inhibition with wortmannin. Pharmacological inhibition of the class I PI3K isoforms alpha, beta, gamma or delta did not affect macrophage LDL-derived cholesterol accumulation or macropinocytosis. Furthermore, macrophages from mice expressing kinase-dead class I PI3K beta, gamma or delta isoforms showed no decrease in cholesterol accumulation or macropinocytosis when compared with wild-type macrophages. Thus, non-class I PI3K isoforms mediated macropinocytosis in these macrophages. Further characterization of the components necessary for LDL uptake, cholesterol accumulation, and macropinocytosis identified dynamin, microtubules, actin, and vacuolar type H(+)-ATPase as

  4. Pemberian Whey-Dangke dalam Air Minum Menekan Kadar Kolesterol, Trigliserida dan Lipoprotein Darah Ayam Broiler

    Directory of Open Access Journals (Sweden)

    Sulmiyati Sulmiyati

    2017-06-01

    Full Text Available Tujuan penelitian untuk mengetahui pengaruh penambahan whey dangke terhadap kadar kolesterol, trigliserida, LDL (low density lipoprotein, HDL (high density lipoprotein, VLDL (very low density lipoprotein darah ayam broiler dan mengukur konsentrasi pemberian whey dangke dalam air minum yang diberikan. Penelitian dilakukan dengan menggunakan Rancangan Acak Lengkap dengan enam perlakuan pemberian whey dangke dalam air minum dengan empat ulangan. Konsentrasi P0 adalah kelompok kontrol 0%; P1=pemberian whey dangke dengan konsentrasi 10%; P2 = pemberian whey dangke dengan konsentrasi 20%; P3 = pemberian whey dangke dengan konsentrasi 30%; P4 = pemberian whey dangke dengan konsentrasi 40%; dan P5 = pemberian whey dangke dengan konsentrasi 50%. Pemberian whey dangke pada ayam broiler strain cobb SR 707 dilakukan selama 15 hari (umur 20–35 hari. Parameter yang diamati adalah kadar kolesterol, trigliserida, LDL, HDL, dan VLDL darah ayam broiler. Data dianalisis dengan analisis sidik ragam, dan jika menunjukkan pengaruh nyata dilanjutkan dengan Uji Beda Nyata Terkecil (BNT. Hasil penelitian menunjukkan bahwa pemberian whey dangke dalam air minum tidak memberikan pengaruh yang nyata (P>0,05 terhadap parameter kolesterol, trigliserida, dan lipoprotein. Namun, terlihat kecenderungan penurunan kadar kolesterol seiring dengan peningkatan konsentrasi pemberian whey dangke. Hasil penelitian dapat disimpulkan bahwa hasil uji in vivo menunjukkan pemberian whey dangke dalam air minum pada ayam broiler pada konsentrasi 50% memperlihatkan penurunan kadar kolesterol hingga 15%. Abstract The purposes of research is to determine the effect of whey dangke against cholesterol levels, triglycerides, LDL, HDL, and VLDL broiler blood and measuring the concentration of whey dangke in water provided. The research was conducted using a completely randomized design with six treatments and four replications. P0 is the control group 0%; P1 = whey dangke added with a concentration

  5. Plasma Cholesteryl Ester Transfer, But Not Cholesterol Esterification, Is Related to Lipoprotein-Associated Phospholipase A(2) : Possible Contribution to an Atherogenic Lipoprotein Profile

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Constantinides, Alexander; Perton, Frank G.; van Leeuwen, Jeroen J. J.; van Pelt, Joost L.; de Vries, Rindert; van Tol, Arie

    Context: Plasma lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density

  6. Apolipoprotein B knockdown by AAV-delivered shRNA lowers plasma cholesterol in mice

    NARCIS (Netherlands)

    Koornneef, Annemart; Maczuga, Piotr; van Logtenstein, Richard; Borel, Florie; Blits, Bas; Ritsema, Tita; van Deventer, Sander; Petry, Harald; Konstantinova, Pavlina

    2011-01-01

    Serum low-density lipoprotein cholesterol (LDL-C) levels are proportionate to the risk of atherosclerotic cardiovascular disease. In order to reduce serum total cholesterol and LDL-C levels in mice, RNA interference (RNAi) was used to inhibit expression of the structural protein of LDL-C,

  7. Low LDL cholesterol, PCSK9 and HMGCR genetic variation, and risk of Alzheimer's disease and Parkinson's disease

    DEFF Research Database (Denmark)

    Benn, Marianne; Nordestgaard, Børge G; Frikke-Schmidt, Ruth

    2017-01-01

    Egger Mendelian randomisation analysis gave a risk ratio for Alzheimer's disease of 0.24 (0.02 to 2.79) for 26 PCSK9 and HMGCR variants, and of 0.64 (0.52 to 0.79) for 380 variants of LDL cholesterol level lowering.Conclusion Low LDL cholesterol levels due to PCSK9 and HMGCR variants had no causal......Objective To test the hypothesis that low density lipoprotein (LDL) cholesterol due to genetic variation in the genes responsible for LDL cholesterol metabolism and biosynthesis(PCSK9 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), respectively) is associated with a high risk of Alzheimer.......79), whereas the corresponding hazard ratios for Alzheimer's disease, vascular dementia, or any dementia did not differ from 1.0. PCSK9 and HMGCR variants combined were associated with a 9.3% lower LDL cholesterol level. In genetic, causal analyses adjusted for age, sex, and year of birth, the risk ratios...

  8. The role of cholesterol metabolism and cholesterol transport in carcinogenesis; A review of scientific findings, relevant to future cancer therapeutics.

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Cruz

    2013-09-01

    Full Text Available While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins, area the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

  9. Macrophage cholesterol efflux correlates with lipoprotein subclass distribution and risk of obstructive coronary artery disease in patients undergoing coronary angiography

    Directory of Open Access Journals (Sweden)

    Kremer Werner

    2009-04-01

    Full Text Available Abstract Background Studies in patients with low HDL have suggested that impaired cellular cholesterol efflux is a heritable phenotype increasing atherosclerosis risk. Less is known about the association of macrophage cholesterol efflux with lipid profiles and CAD risk in normolipidemic subjects. We have therefore measured macrophage cholesterol efflux in142 normolipidemic subjects undergoing coronary angiography. Methods Monocytes isolated from blood samples of patients scheduled for cardiac catheterization were differentiated into macrophages over seven days. Isotopic cholesterol efflux to exogenously added apolipoprotein A-I and HDL2 was measured. Quantitative cholesterol efflux from macrophages was correlated with lipoprotein subclass distribution in plasma from the same individuals measured by NMR-spectroscopy of lipids and with the extent of coronary artery disease seen on coronary angiography. Results Macrophage cholesterol efflux was positively correlated with particle concentration of smaller HDL and LDL particles but not with total plasma concentrations of HDL or LDL-cholesterol. We observed an inverse relationship between macrophage cholesterol efflux and the concntration of larger and triglyceride rich particles (VLDL, chylomicrons. Subjects with significant stenosis on coronary angiography had lower cholesterol efflux from macrophages compared to individuals without significant stenosis (adjusted p = 0.02. Conclusion Macrophage cholesterol efflux is inversely correlated with lipoprotein particle size and risk of CAD.

  10. Niemann-pick type C1 (NPC1) overexpression alters cellular cholesterol homeostasis.

    Science.gov (United States)

    Millard, E E; Srivastava, K; Traub, L M; Schaffer, J E; Ory, D S

    2000-12-08

    The Niemann-Pick type C1 (NPC1) protein is a key participant in intracellular trafficking of low density lipoprotein cholesterol, but its role in regulation of sterol homeostasis is not well understood. To characterize further the function of NPC1, we generated stable Chinese hamster ovary (CHO) cell lines overexpressing the human NPC1 protein (CHO/NPC1). NPC1 overexpression increases the rate of trafficking of low density lipoprotein cholesterol to the endoplasmic reticulum and the rate of delivery of endosomal cholesterol to the plasma membrane (PM). CHO/NPC1 cells exhibit a 1.5-fold increase in total cellular cholesterol and up to a 2.9-fold increase in PM cholesterol. This increase in PM cholesterol is closely paralleled by a 3-fold increase in de novo cholesterol synthesis. Inhibition of cholesterol synthesis results in marked redistribution of PM cholesterol to intracellular sites, suggesting an unsuspected role for NPC1 in internalization of PM cholesterol. Despite elevated total cellular cholesterol, CHO/NPC1 cells exhibit increased cholesterol synthesis, which may be attributable to both resistance to oxysterol suppression of sterol-regulated gene expression and to reduced endoplasmic reticulum cholesterol levels under basal conditions. Taken together, these studies provide important new insights into the role of NPC1 in the determination of the levels and distribution of cellular cholesterol.

  11. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

    Science.gov (United States)

    Toth, Peter P

    2016-01-01

    Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant’s effect on TG levels correlating with the magnitude of the variant’s effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the

  12. Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease.

    Science.gov (United States)

    Toth, Peter P

    2016-01-01

    Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant's effect on TG levels correlating with the magnitude of the variant's effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available

  13. LDL cholesterol estimation in patients with the metabolic syndrome

    OpenAIRE

    Gazi, Irene; Tsimihodimos, Vasilis; Filippatos, Theodosios D; Saougos, Vasilios G; Bairaktari, Eleni T; Tselepis, Alexandros D; Elisaf, Moses

    2006-01-01

    Abstract Background The Friedewald formula (LDL-F) for the estimation of low-density lipoprotein (LDL) cholesterol concentrations is the most often used formula in clinical trials and clinical practice. However, much concern has been raised as to whether this formula is applicable in all patient populations such as the presence of chylomicronaemia and/or hypertriglyceridaemia. The aim of the present study was to evaluate various LDL cholesterol calculation formulas as well as LDL cholesterol ...

  14. Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms

    International Nuclear Information System (INIS)

    Gal, D.; Ohashi, M.; MacDonald, P.C.; Buchsbaum, H.J.; Simpson, E.R.

    1981-01-01

    Cholesterol metabolism was studied in cells from two established gynecologic cancer cell lines which were maintained in monolayer cultures. The cell lines were derived and established from poorly differentiated epidermoid cervical carcinoma and endometrial adenocarcinoma. The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol de novo synthesis, in AC-258 cells was three times higher than that found in EC-50 cells. However, epidermoid cervical cancer cells metabolized low-density lipoprotein, the major transport vehicle for cholesterol in plasma, at a very high rate. This rate is fifteen times greater than the rate observed in fetal adrenal tissue and fifty times greater than the rate observed in nonneoplastic gynecologic tissue, each in organ culture. Both cancer cells in monolayer culture were shown to have specific receptors for LDL. These cancer cells demonstrate no defect in LDL metabolism, and lysosomal degradation of LDL was blocked by chloroquine. From the results of studies of specific binding of LDL in tissues obtained from nude mice it was demonstrated that membrane fractions prepared from EC-50 cells, after propagation in the mice, contained fifteen to thirty times more specific binding capacity for [125I]iodo-LDL than vital organs of the mouse, such as the liver, heart, lung, kidney, or brain. The results of these studies are suggestive that certain tumor cells might have a higher affinity for LDL than normal tissues and cytotoxic drugs or radionucleotides ligated to the LDL macromolecule may be utilized for the specific delivery of these agents

  15. High-Density Lipoproteins and the Immune System

    Directory of Open Access Journals (Sweden)

    Hidesuke Kaji

    2013-01-01

    Full Text Available High-density lipoprotein (HDL plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases.

  16. Site-specific O-glycosylation of members of the low-density lipoprotein receptor superfamily enhances ligand interactions.

    Science.gov (United States)

    Wang, Shengjun; Mao, Yang; Narimatsu, Yoshiki; Ye, Zilu; Tian, Weihua; Goth, Christoffer K; Lira-Navarrete, Erandi; Pedersen, Nis B; Benito-Vicente, Asier; Martin, Cesar; Uribe, Kepa B; Hurtado-Guerrero, Ramon; Christoffersen, Christina; Seidah, Nabil G; Nielsen, Rikke; Christensen, Erik I; Hansen, Lars; Bennett, Eric P; Vakhrushev, Sergey Y; Schjoldager, Katrine T; Clausen, Henrik

    2018-05-11

    The low-density lipoprotein receptor (LDLR) and related receptors are important for the transport of diverse biomolecules across cell membranes and barriers. Their functions are especially relevant for cholesterol homeostasis and diseases, including neurodegenerative and kidney disorders. Members of the LDLR-related protein family share LDLR class A (LA) repeats providing binding properties for lipoproteins and other biomolecules. We previously demonstrated that short linker regions between these LA repeats contain conserved O -glycan sites. Moreover, we found that O -glycan modifications at these sites are selectively controlled by the GalNAc-transferase isoform, GalNAc-T11. However, the effects of GalNAc-T11-mediated O -glycosylation on LDLR and related receptor localization and function are unknown. Here, we characterized O -glycosylation of LDLR-related proteins and identified conserved O -glycosylation sites in the LA linker regions of VLDLR, LRP1, and LRP2 (Megalin) from both cell lines and rat organs. Using a panel of gene-edited isogenic cell line models, we demonstrate that GalNAc-T11-mediated LDLR and VLDLR O -glycosylation is not required for transport and cell-surface expression and stability of these receptors but markedly enhances LDL and VLDL binding and uptake. Direct ELISA-based binding assays with truncated LDLR constructs revealed that O -glycosylation increased affinity for LDL by ∼5-fold. The molecular basis for this observation is currently unknown, but these findings open up new avenues for exploring the roles of LDLR-related proteins in disease. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Effect of apolipoprotein M on high density lipoprotein metabolism and atherosclerosis in low density lipoprotein receptor knock-out mice

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Jauhiainen, Matti; Moser, Markus

    2008-01-01

    To investigate the role of apoM in high density lipoprotein (HDL) metabolism and atherogenesis, we generated human apoM transgenic (apoM-Tg) and apoM-deficient (apoM(-/-)) mice. Plasma apoM was predominantly associated with 10-12-nm alpha-migrating HDL particles. Human apoM overexpression (11-fol...

  18. Modulation of cholesterol transport by maternal hypercholesterolemia in human full-term placenta.

    Directory of Open Access Journals (Sweden)

    Ran Zhang

    Full Text Available The significance of maternal cholesterol transporting to the fetus under normal as well as pathological circumstances is less understood. The objective of this study was to observe the effects of maternal hypercholesterolemia on placental cholesterol transportation. Human full-time placenta, maternal and venous cord blood were sampled at delivery from the pregnant women with serum total cholesterol (TC concentrations at third trimester higher than 7.25 mM (n = 19 and the pregnant women with normal TC concentrations (n = 19. Serum lipids and expression of genes related to cholesterol transportation were measured by western blot or real-time PCR. The results indicated that serum TC, high density lipoprotein cholesterol (HDL-C, and low density lipoprotein cholesterol (LDL-C levels were significantly increased, in pregnancies, but decreased in cord blood in hypercholesterolemic group compared to the matched control group. All the subjects were no-drinking, non-smoker, and gestational disease free. The mRNA expression of lipoprotein receptors, including LDLR and VLDLR were significantly increased, while the protein expression of PCSK9 was significantly increased in hypercholesterolemic placenta. In conclusion, maternal hypercholesterolemia might decrease the transportation of cholesterol from mother to fetus because of the high levels of PCSK9 protein expression.

  19. Serum lipids and lipoproteins in patients with psoriasis.

    Science.gov (United States)

    Taheri Sarvtin, Mehdi; Hedayati, Mohammad Taghi; Shokohi, Tahereh; HajHeydari, Zohreh

    2014-05-01

    Psoriasis is a common chronic and recurrent inflammatory skin disorder characterized by hyperproliferation of keratinocytes and infiltration of T cells, monocytes/macrophages and neutrophils into dermal and epidermal layers of the skin. The prevalence of cardiovascular disorders in these patients is remarkably higher compared to normal individuals, which seems to be associated with the hyperlipidemia. This study was designed and conducted to investigate the serum lipid profile in psoriatic patients and its association with the severity of disease. This case-control study was performed on 50 plaque-type psoriasis patients and 50 healthy individuals as control, matched for age and sex. Blood samples were collected after 14 h fasting. Serum triglyceride, cholesterol and lipoproteins were assayed using the standard kit (made by Pars Azmon Co. Iran). Certain parameters, including serum triglyceride, cholesterol, low density lipoprotein (LDL), and very low density lipoprotein (VLDL), were significantly higher in the case group compared to the controls (P lipoprotein (HDL) was significantly lower in the former (P < 0.001). In addition, there was a significant relationship between severity of psoriasis and serum lipid profile. The results have revealed the higher plasma level of lipids in psoriatic patients. This may elevate the risk of atherosclerosis, particularly cardiovascular disorders. Therefore, from the epidemiological point of view, screening psoriatic patients, particularly those with severe psoriasis, is recommended.

  20. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Nordmann, Alain J; Nordmann, Abigail; Briel, Matthias; Keller, Ulrich; Yancy, William S; Brehm, Bonnie J; Bucher, Heiner C

    2006-02-13

    Low-carbohydrate diets have become increasingly popular for weight loss. However, evidence from individual trials about benefits and risks of these diets to achieve weight loss and modify cardiovascular risk factors is preliminary. We used the Cochrane Collaboration search strategy to identify trials comparing the effects of low-carbohydrate diets without restriction of energy intake vs low-fat diets in individuals with a body mass index (calculated as weight in kilograms divided by the square of height in meters) of at least 25. Included trials had to report changes in body weight in intention-to-treat analysis and to have a follow-up of at least 6 months. Two reviewers independently assessed trial eligibility and quality of randomized controlled trials. Five trials including a total of 447 individuals fulfilled our inclusion criteria. After 6 months, individuals assigned to low-carbohydrate diets had lost more weight than individuals randomized to low-fat diets (weighted mean difference, -3.3 kg; 95% confidence interval [CI], -5.3 to -1.4 kg). This difference was no longer obvious after 12 months (weighted mean difference, -1.0 kg; 95% CI, -3.5 to 1.5 kg). There were no differences in blood pressure. Triglyceride and high-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-carbohydrate diets (after 6 months, for triglycerides, weighted mean difference, -22.1 mg/dL [-0.25 mmol/L]; 95% CI, -38.1 to -5.3 mg/dL [-0.43 to -0.06 mmol/L]; and for high-density lipoprotein cholesterol, weighted mean difference, 4.6 mg/dL [0.12 mmol/L]; 95% CI, 1.5-8.1 mg/dL [0.04-0.21 mmol/L]), but total cholesterol and low-density lipoprotein cholesterol values changed more favorably in individuals assigned to low-fat diets (weighted mean difference in low-density lipoprotein cholesterol after 6 months, 5.4 mg/dL [0.14 mmol/L]; 95% CI, 1.2-10.1 mg/dL [0.03-0.26 mmol/L]). Low-carbohydrate, non-energy-restricted diets appear to be at least as

  1. Association of anti-Mullerian hormone and small-dense low-density lipoprotein cholesterol with hepatosteatosis in young lean women with and without polycystic ovary syndrome.

    Science.gov (United States)

    Oztas, Efser; Caglar, Gamze S; Kaya, Cemil; Karadag, Demet; Demirtas, Selda; Kurt, Mevlut; Pabuccu, Recai

    2014-11-01

    To study the association of anti-Mullerian hormone (AMH) and small-dense low-density lipoprotein cholesterol (sd-LDL) with hepatosteatosis among young, lean, polycystic ovary patients. A prospective, case control study was carried out including 79 young lean women. Fifty-eight women with polycystic ovary syndrome (PCOS) and 21 age-and BMI-matched healthy controls were recruited. Anthropometric variables, biochemical and hormonal parameters, insulin-resistance indices, lipid profiles including sd-LDL levels and serum AMH levels were determined. Hepatic lipid content was evaluated by abdominal ultrasonography (USG). Determining the best predictor(s) which discriminate normal USG and hepatosteatosis was analyzed by multiple logistic regression analyses. Adjusted odds ratios and 95% confidence intervals were also calculated. PCOS patients had an increased prevalence of hepatosteatosis by 41.4% (P = 0.006) and they had significantly higher levels of sd-LDL and AMH when compared with the control group (P lean women with and without PCOS (OR: 2.877, 95%CI: 1.453-5.699, P: 0.02 and OR: 1.336, 95%CI: 1.083-1.648, P: 0.007, respectively). AMH and sd-LDL levels were positively correlated in PCOS patients (r = 0.626, P PCOS group. (OR: 3.347, 95%CI: 1.348-8.313, P = 0.009 and OR: 1.375, 95%CI: 1.072-1.764, P = 0.012, respectively). Statistically significant higher levels of AMH were associated with hepatosteatosis both in insulin resistance (IR) positive and IR negative PCOS patients (P lean PCOS patients. Increased AMH and sd-LDL levels may independently predict hepatosteatosis in young lean women with and without PCOS.

  2. Glycaemic, Blood Pressure and Low Density Lipoprotein Cholesterol Control in Adult Patients with Diabetes in Singapore: A Review of Singapore Literature Over Two Decades.

    Science.gov (United States)

    Poh, Zhongxian; Venkataraman, Kavita; Toh, Sue-Anne Es; Low, Lian Leng

    2017-10-01

    Diabetes mellitus is a burgeoning global health epidemic, with an estimated 422 million people living with diabetes in 2014. The number of adult diabetic patients in Singapore is expected to rise to 1 million in 2050. Despite advances made in the management of diabetes and improvements in healthcare accessibility and delivery, the rate and complications of diabetes (myocardial infarction, stroke, kidney failure and lower limb amputation) in Singapore have not decreased. Gaps between guidelines and practice have been reported in several parts of the world. In this narrative review, we aimed to describe the control of diabetes in Singapore over the past 20 years. We reviewed studies describing, or trials intervening in, the glycaemic, blood pressure (BP) and low density lipoprotein cholesterol (LDL-C) control of adult diabetic patients in Singapore published over the past 20 years (1997-2016). Studies selected from comprehensive electronic databases searches were reviewed by 4 reviewers (2 primary care physicians, 1 diabetologist and 1 public health epidemiologist). The GRADE approach was used to evaluate the quality of evidence. We included 23 articles involving 257,097 subjects. There were 9 longitudinal, 12 cross-sectional and 2 case-control studies. All studies reported mean/median HbA1c between 7.2%-8.6%. BP ranged between 126.5-144 mmHg (systolic) and 70-84 mmHg (diastolic) in 9 studies. Nine studies reported LDL-C between 2.4-3.3 mmol/L. Mirroring global patterns, the glycaemic, BP and LDL-C control in adult diabetic patients in Singapore do not appear to be treated to target in the majority of patients.

  3. Kefir consumption does not alter plasma lipid levels or cholesterol fractional synthesis rates relative to milk in hyperlipidemic men: a randomized controlled trial [ISRCTN10820810

    Science.gov (United States)

    St-Onge, Marie-Pierre; Farnworth, Edward R; Savard, Tony; Chabot, Denise; Mafu, Akier; Jones, Peter JH

    2002-01-01

    Background Fermented milk products have been shown to affect serum cholesterol concentrations in humans. Kefir, a fermented milk product, has been traditionally consumed for its potential health benefits but has to date not been studied for its hypocholesterolemic properties. Methods Thirteen healthy mildly hypercholesterolemic male subjects consumed a dairy supplement in randomized crossover trial for 2 periods of 4 wk each. Subjects were blinded to the dairy supplement consumed. Blood samples were collected at baseline and after 4 wk of supplementation for measurement of plasma total, low-density lipoprotein, and high-density lipoprotein cholesterol and triglyceride concentrations, as well as fatty acid profile and cholesterol synthesis rate. Fecal samples were collected at baseline and after 2 and 4 wk of supplementation for determination of fecal short chain fatty acid level and bacterial content. Results Kefir had no effect on total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglyceride concentrations nor on cholesterol fractional synthesis rates after 4 wk of supplementation. No significant change on plasma fatty acid levels was observed with diet. However, both kefir and milk increased (p < 0.05) fecal isobutyric, isovaleric and propionic acids as well as the total amount of fecal short chain fatty acids. Kefir supplementation resulted in increased fecal bacterial content in the majority of the subjects. Conclusions Since kefir consumption did not result in lowered plasma lipid concentrations, the results of this study do not support consumption of kefir as a cholesterol-lowering agent. PMID:11825344

  4. Caenorhabditis elegans reveals a FxNPxY-independent low-density lipoprotein receptor internalization mechanism mediated by epsin1

    Science.gov (United States)

    Kang, Yuan-Lin; Yochem, John; Bell, Leslie; Sorensen, Erika B.; Chen, Lihsia; Conner, Sean D.

    2013-01-01

    Low-density lipoprotein receptor (LDLR) internalization clears cholesterol-laden LDL particles from circulation in humans. Defects in clathrin-dependent LDLR endocytosis promote elevated serum cholesterol levels and can lead to atherosclerosis. However, our understanding of the mechanisms that control LDLR uptake remains incomplete. To identify factors critical to LDLR uptake, we pursued a genome-wide RNA interference screen using Caenorhabditis elegans LRP-1/megalin as a model for LDLR transport. In doing so, we discovered an unanticipated requirement for the clathrin-binding endocytic adaptor epsin1 in LDLR endocytosis. Epsin1 depletion reduced LDLR internalization rates in mammalian cells, similar to the reduction observed following clathrin depletion. Genetic and biochemical analyses of epsin in C. elegans and mammalian cells uncovered a requirement for the ubiquitin-interaction motif (UIM) as critical for receptor transport. As the epsin UIM promotes the internalization of some ubiquitinated receptors, we predicted LDLR ubiquitination as necessary for endocytosis. However, engineered ubiquitination-impaired LDLR mutants showed modest internalization defects that were further enhanced with epsin1 depletion, demonstrating epsin1-mediated LDLR endocytosis is independent of receptor ubiquitination. Finally, we provide evidence that epsin1-mediated LDLR uptake occurs independently of either of the two documented internalization motifs (FxNPxY or HIC) encoded within the LDLR cytoplasmic tail, indicating an additional internalization mechanism for LDLR. PMID:23242996

  5. Monitoring of high-density lipoprotein cholesterol level is predictive of EGFR mutation and efficacy of EGFR-TKI in patients with advanced lung adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Lv Y

    2016-01-01

    Full Text Available Yang Lv,1,2 Li-Yun Miao,2 Qiu-Fang Chen,1 Yan Li,2 Zhi-Xiang Shi,1 Xuan-Sheng Ding1 1Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2Division of Respiratory Medicine, Department of Respiration, The Affiliated Drum Tower Hospital of Nanjing University Medical College, Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China Abstract: High-density lipoprotein cholesterol (HDL-C has an inverse association with the incidence of lung cancer. However, whether it can be used as a predictive factor in advanced lung adenocarcinoma patients treated with epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKI still remains undefined. This research aimed at studying the relationship of serum HDL-C baseline level and HDL-C kinetics to EGFR mutation, the efficacy of EGFR-TKI, and the predictive value of PFS. The presence of mutation rate in the 192 patients with lung adenocarcinoma was compared within stratified groups. Levels of baseline HDL-C and kinetics of HDL-C were analyzed retrospectively in patients treated with EGFR-TKI harboring EGFR mutation. Univariate and multivariate analyses were performed to investigate the prognostic value of HDL-C. EGFR mutation rate of HDL-C high-level group was significantly higher than that of low-level group (59.0% vs 35.6%, P=0.001. Multivariate logistic analysis showed that high-level HDL-C was an independent predictive factor for EGFR gene mutation (P=0.005; odds ratio =0.417; 95% confidence interval [CI], 0.227–0.768. Patients with a low level of HDL-C before therapy showed a progression of disease in most cases (P<0.001. According to HDL-C kinetics, patients who received EGFR-TKI treatment harboring EGFR mutation were divided into four groups. Univariate analysis showed that patients in nondecreased group had longer progression-free survival (P<0.001; hazard ratio =0.003; 95% CI, 0.001–0.018. Multivariate

  6. Enhanced susceptibility of low-density lipoproteins to oxidation in coronary bypass patients with progression of atherosclerosis

    NARCIS (Netherlands)

    Rijke, Y.B. de; Verwey, H.F.; Vogelezang, C.J.M.; Velde, E.A. van der; Princen, H.M.G.; Laarse, A. van der; Bruschke, A.V.G.; Berkel, T.J.C. van

    1995-01-01

    Oxidation of low-density lipoprotein (LDL) may play a causal role in atherosclerosis. In this study we analyzed whether the severity of progression of coronary atherosclerosis is related to the susceptibility of LDL to oxidative modification. On the basis of repeated coronary angiography, 28

  7. Low-density lipoprotein cholesterol and the risk of cancer: a mendelian randomization study

    DEFF Research Database (Denmark)

    Benn, Marianne; Tybjærg-Hansen, Anne; Stender, Stefan

    2011-01-01

    cholesterol was calculated using the Friedewald equation in samples in which the triglyceride level was less than 354 mg/dL and measured directly by colorimetry for samples with higher triglyceride levels. Risk of cancer was estimated prospectively using Cox proportional hazards regression analyses and cross...

  8. Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents

    DEFF Research Database (Denmark)

    Khetarpal, Sumeet A; Schjoldager, Katrine T; Christoffersen, Christina

    2016-01-01

    Human genetics studies have implicated GALNT2, encoding GalNAc-T2, as a regulator of high-density lipoprotein cholesterol (HDL-C) metabolism, but the mechanisms relating GALNT2 to HDL-C remain unclear. We investigated the impact of homozygous GALNT2 deficiency on HDL-C in humans and mammalian mod...

  9. Heparin induces an accumulation of atherogenic lipoproteins during hemodialysis in normolipidemic end-stage renal disease patients.

    Science.gov (United States)

    Barbagallo, Carlo M; Noto, Davide; Cefalù, Angelo B; Ganci, Antonia; Giammarresi, Carlo; Panno, Donata; Cusumano, Gaspare; Greco, Massimiliano; Di Gaudio, Francesca; Averna, Maurizio R

    2015-07-01

    Dyslipidemias may account for the excess of cardiovascular mortality in end-stage renal disease (ESRD). Lipoprotein studies in ESRD patients are usually relative to prehemodialysis samples even if significative changes may occur after dialysis. In this study, we aimed to investigate the effects of ESRD on triglyceride-rich lipoproteins (TRL) subpopulations distribution and acute change following hemodialytic procedures, including the relative contribution of heparin administration. We selected a group of normolipidemic male middle-aged ESRD patients free of any concomitant disease affecting lipoprotein remnant metabolism compared with controls. We separated TRL subfractions according to density and apoE content and evaluated the changes of these particles after hemodialytic procedures with or without heparin. ESRD subjects had higher TRL subfractions, with the exception of apoE-rich particles, lower high-density lipoprotein (HDL) largest subclasses, and a smaller low-density lipoprotein peak particle size than controls. After a hemodialytic standard procedure with heparin, we demonstrated a significant reduction of triglyceride, an increase of HDL-cholesterol levels, and a raise of small very-low-density lipoprotein, intermediate-density lipoproteins (IDL), apoE-rich particles, and non-HDL-cholesterol levels. When hemodialysis was performed without heparin, no significant changes were observed. In the absence of concomitant hyperlipidemic triggers, ESRD patients show significant lipoprotein abnormalities before dialysis, but without any increased remnant particles concentrations. We speculate that hemodialysis, in particular heparin administration during this procedure, leads to a massive atherogenic TRLs production because of the acute stimulation of the dysfunctional lipolytic system not followed by an efficient removal, determining a recurrent lipoprotein remnant accumulation. © 2014 International Society for Hemodialysis.

  10. The effect of interaction between Lipoprotein Lipase and ApoVLDL-II ...

    African Journals Online (AJOL)

    GREGO

    2007-04-02

    Apr 2, 2007 ... correlation between growth and fitness is not absolute, it ... significant differences are found in the plasma triglyceride ... (VLDL) and high density lipoprotein (HDL) concentration ... High-density lipoprotein cholesterol was.

  11. Serum low-density lipoprotein cholesterol level is strong risk factor for acquired color vision impairment in young to middle-aged Japanese men: the Okubo Color Study Report 2.

    Science.gov (United States)

    Shoji, Takuhei; Sakurai, Yutaka; Sato, Hiroki; Chihara, Etsuo; Ishida, Masahiro; Omae, Kazuyuki

    2010-06-01

    To investigate associations between blood low-density lipoprotein cholesterol (LDL-C) levels and the prevalence of acquired color vision impairment (ACVI) in middle-aged Japanese men. Participants in this cross-sectional study underwent color vision testing, ophthalmic examination, a standardized interview and examination of venous blood samples. Ishihara plates, a Lanthony 15-hue desaturated panel, and Standard pseudoisochromatic Plates part 2 were used to examine color vision ability. The Farnsworth-Munsell 100-hue test was performed to define ACVI. Smoking status and alcohol intake were recorded during the interview. We performed logistic regression analysis adjusted for age, LDL-C level, systemic hypertension, diabetes, cataract, glaucoma, overweight, smoking status, and alcohol intake. Adjusted odds ratios for four LDL-C levels were calculated. A total of 1042 men were enrolled, 872 participants were eligible for the study, and 31 subjects were diagnosed with ACVI. As compared to the lowest LDL-C category level (or=160 mg/dl). The multiple-adjusted ORs were 2.91 (95% CI, 0.87-9.70) for the 2nd highest category and 3.81 (95% CI, 1.03-14.05) for the highest level. Tests for trend were significant (Pmen with elevated LDL-C levels. These changes might be related to deteriorated neurologic function associated with lipid metabolite abnormalities. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  12. Effect of different fat-enriched meats on non-cholesterol sterols and oxysterols as markers of cholesterol metabolism: Results of a randomized and cross-over clinical trial.

    Science.gov (United States)

    Baila-Rueda, L; Mateo-Gallego, R; Pérez-Calahorra, S; Lamiquiz-Moneo, I; de Castro-Orós, I; Cenarro, A; Civeira, F

    2015-09-01

    Different kinds of fatty acids can affect the synthesis, absorption, and elimination of cholesterol. This study was carried out to assess the associations of cholesterol metabolism with the intake of two meats with different fatty acid composition in healthy volunteers. The study group was composed of 20 subjects (12 males and eight females; age, 34.4 ± 11.6 years; body mass index (BMI), 23.5 ± 2.3 kg/m(2); low-density lipoprotein (LDL) cholesterol, 2.97 ± 0.55 mmol/l; high-density lipoprotein (HDL) cholesterol, 1.61 ± 0.31 mmol/l; triglycerides (TG), 1.06 ± 0.41 mmol/l) who completed a 30-day randomized and cross-over study to compare the cholesterol metabolism effect of 250 g of low-fat lamb versus 250 g of high-fat lamb per day in their usual diet. Cholesterol absorption, synthesis, and elimination were estimated from the serum non-cholesterol sterol and oxysterol concentrations analyzed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). No changes in weight, plasma lipids, or physical activity were observed across the study. Cholesterol intestinal absorption was decreased with both diets. Cholesterol synthesis and elimination decreased during the low-fat lamb dietary intervention (ρ = 0.048 and ρ = 0.005, respectively). Acute changes in the diet fat content modify the synthesis, absorption, and biliary elimination of cholesterol. These changes were observed even in the absence of total and LDL cholesterol changes in plasma. ClinicalTrials.gov PRS, NCT02259153. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides

    International Nuclear Information System (INIS)

    Qureshi, Rashid Nazir; Kok, Wim Th.; Schoenmakers, Peter J.

    2009-01-01

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples.

  14. Fractionation of human serum lipoproteins and simultaneous enzymatic determination of cholesterol and triglycerides

    Energy Technology Data Exchange (ETDEWEB)

    Qureshi, Rashid Nazir [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Kok, Wim Th., E-mail: W.Th.Kok@uva.nl [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands); Schoenmakers, Peter J. [Polymer-Analysis Group, van' t Hoff Institute for Molecular Sciences, University of Amsterdam, Nieuwe Achtergracht 166, 1018WV Amsterdam (Netherlands)

    2009-11-03

    A method based on Asymmetric Flow Field-Flow Fractionation (AF4) was developed to separate different types of lipoproteins from human serum. The emphasis in the method optimization was on the possibilities to characterize the largest lipoprotein fractions (LDL and VLDL), which is usually not possible with the size-exclusion chromatography methods applied in routine analysis. Different channel geometries and flow programs were tested and compared. The use of a short fractionation channel was shown to give less sample dilution at the same fractionation power compared to a conventional, long channel. Different size selectivities were obtained with an exponential decay and a linear cross flow program. The ratio of the UV absorption signal to the light scattering signal was used to validate the relation between retention time and size of the fractionated particles. An experimental setup was developed for the simultaneous determination of the cholesterol and triglycerides distribution over the lipoprotein fractions, based on enzymatic reactions followed by UV detection at 500 nm. Coiled and knitted PTFE tubing reactors were compared. An improved peak sharpness and sensitivity were observed with the knitted tubing reactor. After optimization of the experimental conditions a satisfactory linearity and precision (2-3% rsd for cholesterol and 5-6% rsd for triglycerides) were obtained. Finally, serum samples, a pooled sample from healthy volunteers and samples of sepsis patients, were analyzed with the method developed. Lipoprotein fractionation and cholesterol and triglyceride distributions could be correlated with the clinical background of the samples.

  15. Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction

    DEFF Research Database (Denmark)

    Langsted, A.; Freiberg, J.J.; Nordestgaard, Børge

    2008-01-01

    BACKGROUND: Lipid profiles are usually measured after fasting. We tested the hypotheses that these levels change only minimally in response to normal food intake and that nonfasting levels predict cardiovascular events. METHODS AND RESULTS: We cross-sectionally studied 33 391 individuals 20 to 95...... to HDL cholesterol, and ratio of apolipoprotein B to apolipoprotein A1 did not change in response to normal food intake. The maximum changes after normal food and fluid intake from fasting levels were -0.2 mmol/L for total cholesterol, -0.2 mmol/L for low-density lipoprotein cholesterol, -0.1 mmol...... years of age from the Copenhagen General Population Study. We also studied 9319 individuals 20 to 93 years of age from the Copenhagen City Heart Study, 1166 of whom developed cardiovascular events during 14 years of follow-up. Compared with fasting levels, total cholesterol, low-density lipoprotein...

  16. Effects of High Fat Feeding and Diabetes on Regression of Atherosclerosis Induced by Low-Density Lipoprotein Receptor Gene Therapy in LDL Receptor-Deficient Mice.

    Directory of Open Access Journals (Sweden)

    Florian Willecke

    Full Text Available We tested whether a high fat diet (HFD containing the inflammatory dietary fatty acid palmitate or insulin deficient diabetes altered the remodeling of atherosclerotic plaques in LDL receptor knockout (Ldlr-/- mice. Cholesterol reduction was achieved by using a helper-dependent adenovirus (HDAd carrying the gene for the low-density lipoprotein receptor (Ldlr; HDAd-LDLR. After injection of the HDAd-LDLR, mice consuming either HFD, which led to insulin resistance but not hyperglycemia, or low fat diet (LFD, showed regression compared to baseline. However there was no difference between the two groups in terms of atherosclerotic lesion size, or CD68+ cell and lipid content. Because of the lack of effects of these two diets, we then tested whether viral-mediated cholesterol reduction would lead to defective regression in mice with greater hyperglycemia. In both normoglycemic and streptozotocin (STZ-treated hyperglycemic mice, HDAd-LDLR significantly reduced plasma cholesterol levels, decreased atherosclerotic lesion size, reduced macrophage area and lipid content, and increased collagen content of plaque in the aortic sinus. However, reductions in anti-inflammatory and ER stress-related genes were less pronounced in STZ-diabetic mice compared to non-diabetic mice. In conclusion, HDAd-mediated Ldlr gene therapy is an effective and simple method to induce atherosclerosis regression in Ldlr-/- mice in different metabolic states.

  17. Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

    Directory of Open Access Journals (Sweden)

    Cédric Delporte

    2013-01-01

    Full Text Available Oxidation of low-density lipoprotein (LDL has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

  18. Effects of Ginger on Serum Lipids and Lipoproteins in Peritoneal Dialysis Patients: A Randomized Controlled Trial.

    Science.gov (United States)

    Tabibi, Hadi; Imani, Hossein; Atabak, Shahnaz; Najafi, Iraj; Hedayati, Mehdi; Rahmani, Leila

    2016-01-01

    ♦ In peritoneal dialysis (PD) patients, one of the major risk factors for cardiovascular disease is lipid abnormalities. This study was designed to investigate the effects of ginger supplementation on serum lipids and lipoproteins in PD patients. ♦ In this randomized, double-blind, placebo-controlled trial, 36 PD patients were randomly assigned to either the ginger or the placebo group. The patients in the ginger group received 1,000 mg ginger daily for 10 weeks, while the placebo group received corresponding placebos. At baseline and at the end of week 10, 7 mL of blood were obtained from each patient after a 12- to 14-hour fast, and serum concentrations of triglyceride, total cholesterol, low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and lipoprotein (a) [Lp (a)] were measured. ♦ Serum triglyceride concentration decreased significantly up to 15% in the ginger group at the end of week 10 compared with baseline (p ginger reduces serum triglyceride concentration, which is a risk factor for cardiovascular disease, in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

  19. Common Low-Density Lipoprotein Receptor p.G116S Variant Has a Large Effect on Plasma Low-Density Lipoprotein Cholesterol in Circumpolar Inuit Populations

    DEFF Research Database (Denmark)

    Dube, J. B.; Wang, J.; Cao, H.

    2015-01-01

    .G116S and p.R730W. METHODS AND RESULTS: Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6x...

  20. Effect of doxazosin on cholesterol synthesis in cell culture

    International Nuclear Information System (INIS)

    D'Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent

  1. Prevalence of low HDL-cholesterol in patients with cardiovascular risk factors: The ECHOS (Etude du Cholesterol HDL en Observationnel) French Survey.

    Science.gov (United States)

    Farnier, M; Garnier, P; Yau, C; Dejager, S; Verpilleux, M P

    2006-10-01

    A low concentration of high-density lipoprotein-cholesterol (HDL-C) is an independent risk factor for cardiovascular heart disease (CHD), but little is known about the distribution of HDL-C in France. This study evaluated the prevalence of low HDL-C among a large French population (5232 patients) with other cardiovascular risk factors. Depending on the guidelines used, the prevalence of low HDL-C varied from 8.7% (cutoff value of 35 mg/dl) to 26.9% (National Cholesterol Education Program metabolic syndrome cutoff values). The prevalence of low HDL-C gradually increased with the number of associated risk factors. We identified three independent risk predictors for low HDL-C: hypertriglyceridaemia (HTG), abdominal obesity and gender. Overall, the frequency of HDL-C assessment was very high (>85%) and it was highest in patients with hypercholesterolaemia or a history of CHD. Risk factors more frequently associated with low HDL-C (i.e. HTG, abdominal obesity and type 2 diabetes) were not associated with a more frequent assessment of HDL-C. Our findings indicate that in France, the prevalence of low HDL-C remains relatively high, particularly for patients with obesity and HTG.

  2. The monocyte counts to HDL cholesterol ratio in obese and lean patients with polycystic ovary syndrome.

    Science.gov (United States)

    Usta, Akin; Avci, Eyup; Bulbul, Cagla Bahar; Kadi, Hasan; Adali, Ertan

    2018-04-10

    Women with polycystic ovary syndrome are more likely to suffer from obesity, insulin resistance, and chronic low-grade inflammation. In fact, the excessive activation of monocytes exacerbates oxidative stress and inflammation. However, high-density lipoprotein cholesterol neutralizes the pro-inflammatory and pro-oxidant effects of monocytes. The aim of this study is to investigate whether monocyte counts to high-density lipoprotein cholesterol ratio can predict the inflammatory condition in patients with polycystic ovary syndrome. In this cross-sectional study, a total of 124 women (61 of them with polycystic ovary syndrome and 63 age-matched healthy volunteers) were included in the study population. Obese polycystic ovary syndrome patients (n = 30) with a body mass index of ≥25 kg/m 2 and lean polycystic ovary syndrome patients (n = 31) with a body mass index of polycystic ovary syndrome were significantly higher than in control subjects (p = 0.0018). Moreover, a regression analysis revealed that body mass index, the homeostasis model assessment of insulin resistance and the high sensitivity C-reactive protein levels were confounding factors that affected the monocyte counts to high density lipoprotein cholesterol values. Additionally, a univariate and multivariate logistic regression analysis demonstrated that the increased monocyte counts to high density lipoprotein cholesterol values were more sensitive than the other known risk factors (such as increased body mass index, homeostasis model assessment of insulin resistance and high sensitive C-reactive protein levels) in the prediction of the inflammation in patients with polycystic ovary syndrome. The present study demonstrated that the monocyte count to high density lipoprotein cholesterol may be a novel and useful predictor of the presence of polycystic ovary syndrome.

  3. Ten years of lipoprotein apheresis for familial hypercholesterolemia in Malaysia: A creative approach by a cardiologist in a developing country

    NARCIS (Netherlands)

    Khoo, Kah Lin; Page, Michael M.; Liew, Yin Mei; Defesche, Joep C.; Watts, Gerald F.

    2016-01-01

    Familial hypercholesterolemia (FH) leads to premature coronary artery disease and aortic stenosis, with undertreated severe forms causing death at a young age. Lipoprotein apheresis (LA) is often required for lowering low-density lipoprotein cholesterol levels in severe FH. The objective of this

  4. Loci of catabolism of beta-very low density lipoprotein in vivo delineated with a residualizing label, 125I-dilactitol tyramine

    International Nuclear Information System (INIS)

    Daugherty, A.; Thorpe, S.R.; Lange, L.G.; Sobel, B.E.; Schonfeld, G.

    1985-01-01

    beta-Very low density lipoprotein (beta-VLDL) may be a major atherogenic lipoprotein, and knowledge of the sites of its catabolism should facilitate elucidation of mechanisms important in the regulation of its plasma concentrations. In this study, catabolic sites of beta-VLDL have been delineated in normolipidemic rabbits with a novel, radioiodinated, residualizing label, 125 I-dilactitol tyramine ( 125 I-DLT). Comparative studies of beta-VLDL and low density lipoprotein catabolism were performed with 125 I-DLT conjugated to each lipoprotein and with lipoproteins iodine-labeled conventionally. Conjugation did not alter size distributions or charge characteristics of lipoprotein particles. The overall processing (binding and degradation) of lipoproteins by cultured rabbit skin fibroblasts was not influenced by 125 I-DLT derivatization, suggesting that attachment of the label did not influence cell receptor-lipoprotein interactions. Furthermore, although degradation products of 125 I-lipoproteins leaked out of the cells and into the medium, the degradation products of 125 I-DLT lipoproteins were retained by the cells. The principal catabolic site of beta-VLDL in normolipidemic rabbits was found to be the liver with 54 +/- 4% of injected 125 I retained in this organ 24 h after injection of 125 I-DLT-beta-VLDL. When catabolism was normalized to tissue weight, the liver and adrenals were found to be approximately equally active in the metabolism of beta-VLDL. In agreement with results of other studies with residualizing labels, the principal organ of catabolism of 125 I-DLT-LDL in vivo was the liver. The adrenals were the most highly catabolizing organ when results were normalized for tissue weight

  5. Effects of obesity and body fat distribution on lipids and lipoproteins in nondiabetic American Indians: The Strong Heart Study.

    Science.gov (United States)

    Hu, D; Hannah, J; Gray, R S; Jablonski, K A; Henderson, J A; Robbins, D C; Lee, E T; Welty, T K; Howard, B V

    2000-09-01

    To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/ lipoproteins. Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m2) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m2), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = -0.24, p HDL cholesterol (r = -0.23, p correlated with triglycerides (r = 0.30, p correlated with HDL cholesterol (r = -0.35, p HDL cholesterol decreased with waist circumference (r = -0.36, p correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (-1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (-0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All

  6. Increased fluidity and oxidation of malarial lipoproteins: relation with severity and induction of endothelial expression of adhesion molecules

    Directory of Open Access Journals (Sweden)

    Looareesuwan Sornchai

    2004-06-01

    Full Text Available Abstract Introduction Oxidative stress has been demonstrated in malaria. The potential oxidative modification of lipoproteins derived from malaria patients was studied. These oxidized lipids may have role in pathogenesis of malaria. Method The plasma lipid profile and existence of oxidized forms of very low density lipoprotein (VLDL, low density lipoprotein (LDL and high density lipoprotein (HDL were investigated in malaria (17 mild and 24 severe patients and 37 control subjects. Thiobarbituric acid reactive substances (TBARs, conjugated dienes, tryptophan fluorescence and fluidity of lipoproteins were determined as markers of oxidation. The biological effect of malarial lipoproteins was assessed by the expression of adhesion molecules on endothelial cells. Results Malarial lipoproteins had decreased cholesterol (except in VLDL and phospholipid. The triglyceride levels were unchanged. The cholesterol/phospholipid ratio of LDL was decreased in malaria, but increased in VLDL and HDL. TBARs and conjugate dienes were increased in malarial lipoproteins, while the tryptophan fluorescence was decreased. The fluidity of lipoproteins was increased in malaria. These indicated the presence of oxidized lipoproteins in malaria by which the degree of oxidation was correlated with severity. Of three lipoproteins from malarial patients, LDL displayed the most pronounced oxidative modification. In addition, oxidized LDL from malaria patients increased endothelial expression of adhesion molecules. Conclusion In malaria, the lipoproteins are oxidatively modified, and the degree of oxidation is related with severity. Oxidized LDL from malarial patients increases the endothelial expression of adhesion molecules. These suggest the role of oxidized lipoproteins, especially LDL, on the pathogenesis of disease.

  7. [Relationship between Ghrelin polymorphism and serum lipoprotein levels in Han Chinese with or without coronary heart disease risk factors].

    Science.gov (United States)

    Xie, Xuan; Zhang, Jing; Wang, Yu-huan; Wang, Jun-hong; Zhang, Chun-hong; Ni, Hong-yan; Yuan, Xiao-hong

    2008-04-01

    To investigate the relationship between polymorphism of Ghrelin gene and serum levels of lipoprotein in Han Chinese with or without coronary heart disease (CHD) risk factors. PCR restriction fragment length polymorphism assay was used to detect the distribution of genotypes of Ghrelin gene in 225 Han Chinese (40 to 69 years-old) with CHD risk factors, 78 subjects without CHD risk factors served as normal controls. Serum levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C) and very low-density lipoprotein (VLDL) were measured to analyze the relationship with the polymorphism of Ghrelin gene. Ghrelin genotype frequencies of AA, AG, GG (0.975, 0.025, 0.00 in control group and 0.956, 0.040, 0.004 in the high-risk group, all P > 0.05) as well as the allele frequencies of A, G (0.987, 0.013 in control group and 0.976, 0.024 in the high-risk group, all P > 0.05) were similar between the groups. HDL-C levels of the Arg/Gln carriers were significantly lower than those of Arg/Arg carriers in control group and in the high-risk group (all P < 0.05). Arg/Gln carriers were associated lower HDL-C levels in Han Chinese.

  8. Low-Density Lipoprotein Receptor-Related Protein 6 (LRP6 Is a Novel Nutritional Therapeutic Target for Hyperlipidemia, Non-Alcoholic Fatty Liver Disease, and Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Gwang-woong Go

    2015-06-01

    Full Text Available Low-density lipoprotein receptor-related protein 6 (LRP6 is a member of the low-density lipoprotein receptor family and has a unique structure, which facilitates its multiple functions as a co-receptor for Wnt/β-catenin signaling and as a ligand receptor for endocytosis. The role LRP6 plays in metabolic regulation, specifically in the nutrient-sensing pathway, has recently garnered considerable interest. Patients carrying an LRP6 mutation exhibit elevated levels of LDL cholesterol, triglycerides, and fasting glucose, which cooperatively constitute the risk factors of metabolic syndrome and atherosclerosis. Since the discovery of this mutation, the general role of LRP6 in lipid homeostasis, glucose metabolism, and atherosclerosis has been thoroughly researched. These studies have demonstrated that LRP6 plays a role in LDL receptor-mediated LDL uptake. In addition, when the LRP6 mutant impaired Wnt-LRP6 signaling, hyperlipidemia, non-alcoholic fatty liver disease, and atherosclerosis developed. LRP6 regulates lipid homeostasis and body fat mass via the nutrient-sensing mechanistic target of the rapamycin (mTOR pathway. Furthermore, the mutant LRP6 triggers atherosclerosis by activating platelet-derived growth factor (PDGF-dependent vascular smooth muscle cell differentiation. This review highlights the exceptional opportunities to study the pathophysiologic contributions of LRP6 to metabolic syndrome and cardiovascular diseases, which implicate LRP6 as a latent regulator of lipid metabolism and a novel therapeutic target for nutritional intervention.

  9. Low-density Lipoprotein Improves Motility and Plasma Membrane Integrity of Cryopreserved Canine Epididymal Spermatozoa

    OpenAIRE

    N. Prapaiwan; T. Tharasanit; S. Punjachaipornpol; D. Yamtang; A. Roongsitthichai; W. Moonarmart; K. Kaeoket; S. Manee-in

    2016-01-01

    Cryopreservation of caudal epididymal spermatozoa is an effective technique to conserve genetic potentials of superior dogs when it is not possible to collect ejaculated spermatozoa. Although hen egg yolk is commonly supplemented into the semen extender, active substances within the egg yolk which protect sperm against cryoinjury remain to be discovered. Among its compositions, low-density lipoprotein (LDL) has been reported to have a cryoprotective property for sperm cryopreservation. Howeve...

  10. Plasma lipoprotein(a levels: a comparison between diabetic and non-diabetic patients with acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Holanda Maurus Marques de Almeida

    2004-01-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate lipoprotein(a (Lp(a, total cholesterol, high density lipoprotein cholesterol (HDL, low density lipoprotein cholesterol (LDL, very low density lipoprotein cholesterol (VLDL , triglycerides , apolipoprotein A (apo A and B100 (apo B100, uric acid, glycaemic and insulin plasmatic concentrations in patients affected by acute stroke. In this group of patients, we have compared the variables between type 2 diabetic patients and non-diabetic patients. METHOD: We evaluate a total of 34 non-diabetic patients (22 males and 12 females; mean age 66.71 ± 10.83 years and a group of 26 type 2 diabetic patients (15 males and 11 females; mean age 66.35 ± 9.92 years in a cross-sectional study. RESULTS: Mean Lp(a concentration did not significantly differ between type 2 diabetic patients and non-diabetic subjects (29.49 ± 23.09 vs 44.81 ± 44.34 mg/dl. The distribution of Lp(alevels was highly skewed towards the higher levels in both groups, being over 30 mg/dl in 50%. Lp(a concentration was positively correlated with abdominal adiposity, using waist-hip ratio(WHR(p< 0.05. No association was found between Lp(a and others risk factors like sex, age, other lipidic parameters and the presence of stroke. CONCLUSIONS: Our results showed that there were no significant differences between diabetic and non-diabetic patients' serum Lp(a levels, which indicates that elevated Lp(a levels were associated with ischemic stroke, irrespective of the presence of type 2 diabetes mellitus (type 2 DM.

  11. High-density lipoproteins: a novel therapeutic target for cardiovascular disease

    Directory of Open Access Journals (Sweden)

    TS Mohamed Saleem

    2011-01-01

    Full Text Available TS Mohamed Saleem1, PV Sandhya Rani1, K Gauthaman21Department of Pharmacology, Annamacharya College of Pharmacy, New Boyanapalli, Andhrapradesh, India; 2Department of Drug Technology, Faculty of Medical Technology, Derna, LibyaAbstract: Cardiovascular disease has a high rate of mortality in both Western and developing countries. Atherosclerosis and generation of reactive oxygen species through oxidative stress is the major risk factor for cardiovascular disease. Atherothrombosis with low levels of high-density lipoprotein (HDL and high levels of low-density lipoprotein is a major risk factor for atherosclerosis-induced cardiovascular disease. Lipid-lowering drugs like statins, niacin, fibrates, and some newer agents, ie, the apolipoprotein A-I mimetics and the cholesteryl ester transfer protein inhibitors, not only increase HDL levels but are also effective in reducing key atherogenic lipid components, including triglyceride-rich lipoproteins. The aim of this review is to discuss the accumulating evidence suggesting that HDL possesses a diverse range of biological actions, and that increasing HDL levels by drug treatment may be beneficial in the prevention of cardiovascular disease.Keywords: cardiovascular disease, lipoproteins, statins, apolipoprotein, atherosclerosis

  12. Konsumsi Daging Sapi Bali Dan Pengaruhnya Pada Profil Lipoprotein Plasma Tikus (CONSUMPTION OF BEEF BALI CATTLE AND IT’S EFFECTS ON RATS PLASMA LIPOPROTEIN PROFILE

    Directory of Open Access Journals (Sweden)

    I Nyoman Suarsana

    2016-02-01

    Full Text Available Consumption of beef in Indonesia is continuously increasing. Aside from being a source of protein, beef also contains all essential amino acids, vitamins, fats and cholesterol making it an ideal choice for consumers. This study aims to analyze the consumption of beef bali on rats plasma lipoprotein levels. A total of 15 male rats Spraque Dawlly average body weight of 90-100g was used in this study. They were sub-divided into five  groups: a control group, without treatment (I, fed- beef group was treated from 7th day (II,  fed-beef group was treated from 5th day (III,  fed-beef group was treated from 3th day (IV, and fed-beef group was treated from 1st day (V.  At the end of the experiment, i.e 9th days all groups of rats were euthanasia with cethamine-HCl. Blood was taken through the heart and placed in tubes containing EDTA to obtain plasma. Levels of  cholesterol, triglycerides,  HDL was analyzed by spectrophotometric method using cholesterol KIT (Ref10028, TGA (Ref10720P, and HDL (Ref10018. LDL levels were calculated using the formula: LDL= total cholesterol-(TG/5-HDL. The results showed that  rats  given beef bali cattle for 8 days was lead to increased plasma triglyceride levels significantly (P<0.05, while cholesterol, HDL (high density lipoprotein and LDL (low density lipoprotein plasma levels is not increased.

  13. Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation

    International Nuclear Information System (INIS)

    Lee, Ha Young; Kim, Sang Doo; Baek, Suk-Hwan; Choi, Joon Hyuk; Cho, Kyung-Hyun; Zabel, Brian A.; Bae, Yoe-Sik

    2013-01-01

    Highlights: ► SAA induced macrophage foam cell formation. ► SAA stimulated upregulation of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1). ► SAA-induced LOX1 expression and foam cell formation is mediated by JNK/NF-κB signaling. ► HDL-conjugated SAA also stimulates foam cell formation via LOX1 upregulation. ► The finding reveals a novel mechanism of action of SAA in the pathogenesis of atherosclerosis. -- Abstract: Elevated levels of serum amyloid A (SAA) is a risk factor for cardiovascular diseases, however, the role of SAA in the pathophysiology of atherosclerosis remains unclear. Here we show that SAA induced macrophage foam cell formation. SAA-stimulated foam cell formation was mediated by c-jun N-terminal kinase (JNK) signaling. Moreover, both SAA and SAA-conjugated high density lipoprotein stimulated the expression of the important scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) via nuclear factor-κB (NF-κB). A LOX1 antagonist carrageenan significantly blocked SAA-induced foam cell formation, indicating that SAA promotes foam cell formation via LOX1 expression. Our findings therefore suggest that SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis

  14. Serum amyloid A stimulates macrophage foam cell formation via lectin-like oxidized low-density lipoprotein receptor 1 upregulation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ha Young, E-mail: hayoung@skku.edu [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Kim, Sang Doo [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Baek, Suk-Hwan [Department of Biochemistry and Molecular Biology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Choi, Joon Hyuk [Department of Pathology, College of Medicine, Yeungnam University, Daegu 705-717 (Korea, Republic of); Cho, Kyung-Hyun [School of Biotechnology, Yeungnam University, Gyeongsan 712-749 (Korea, Republic of); Zabel, Brian A. [Palo Alto Institute for Research and Education, Veterans Affairs Hospital, Palo Alto, CA 94304 (United States); Bae, Yoe-Sik, E-mail: yoesik@skku.edu [Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Mitochondria Hub Regulation Center, Dong-A University, Busan 602-714 (Korea, Republic of); Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of)

    2013-03-29

    Highlights: ► SAA induced macrophage foam cell formation. ► SAA stimulated upregulation of lectin-like oxidized low-density lipoprotein receptor 1 (LOX1). ► SAA-induced LOX1 expression and foam cell formation is mediated by JNK/NF-κB signaling. ► HDL-conjugated SAA also stimulates foam cell formation via LOX1 upregulation. ► The finding reveals a novel mechanism of action of SAA in the pathogenesis of atherosclerosis. -- Abstract: Elevated levels of serum amyloid A (SAA) is a risk factor for cardiovascular diseases, however, the role of SAA in the pathophysiology of atherosclerosis remains unclear. Here we show that SAA induced macrophage foam cell formation. SAA-stimulated foam cell formation was mediated by c-jun N-terminal kinase (JNK) signaling. Moreover, both SAA and SAA-conjugated high density lipoprotein stimulated the expression of the important scavenger receptor lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) via nuclear factor-κB (NF-κB). A LOX1 antagonist carrageenan significantly blocked SAA-induced foam cell formation, indicating that SAA promotes foam cell formation via LOX1 expression. Our findings therefore suggest that SAA stimulates foam cell formation via LOX1 induction, and thus likely contributes to atherogenesis.

  15. Comparison of calculated versus directly-measured low-density lipoprotein-cholesterol: An evaluation of ten formulas for an HIV-positive population in Sub-Saharan Africa.

    Science.gov (United States)

    Osegbe, Ifeyinwa; Ugonabo, Martin; Chukwuka, Chinwe; Meka, Ijeoma; Nwosu, Nnamdi

    2017-01-01

    Low-density lipoprotein cholesterol (LDLC) is a modifiable risk factor for atherosclerotic cardiovascular disease, therefore needs to be assessed and monitored. Direct homogeneous assays and various formulas exist to determine LDLC. We aimed to compare the directly measured LDL (dLDLC) with ten formulas for estimating LDLC. This was a 2-year retrospective study of fasting lipid profile results obtained from HIV-positive patients attending an outpatient clinic at the University of Nigeria Teaching Hospital, Enugu, Nigeria, using homogeneous direct assays. Estimated LDLC was determined using ten formulas. Pearson's correlation, Bland-Altman plots, and linear regression were performed. Statistical significance was P < 0.05. Three thousand four hundred and eighty-two lipid results with mean ± standard deviation (SD) dLDLC of 2.1 ± 1.1 mmol/L were included in this study. There was a strong, positive correlation between Friedewald's LDLC and dLDLC n = 3412, r = 0.84, P < 0.001, but linear regression demonstrated a proportional bias P = 0.005. Ahmadi's equation showed the worst correlation n = 3482, r = 0.35, P < 0.001, but when applied to samples with triglyceride (TG) <1.13 mmol/L (100 mg/dl), the correlation showed a strong, positive relationship n = 1395, r = 0.80, P < 0.001, and no proportional bias P = 0.86. Teerankanchana's equation was the only formula that showed no difference between its LDLC and dLDLC ( n = 3482, P = 0.056). It also demonstrated strong, positive correlation ( n = 3482, r = 0.84, P < 0.001) and had a mean difference ± SD of -0.68 ± 0.63. Teerankanchana's formula showed good correlation and minimal bias with dLDLC at all TG levels. Moreover, linear regression showed no difference in the two. It seems to be the most suitable formula for estimating LDLC in our HIV-positive population.

  16. Use of health information technology (HIT) to improve statin adherence and low-density lipoprotein cholesterol goal attainment in high-risk patients: proceedings from a workshop.

    Science.gov (United States)

    Cohen, Jerome D; Aspry, Karen E; Brown, Alan S; Foody, Joanne M; Furman, Roy; Jacobson, Terry A; Karalis, Dean G; Kris-Etherton, Penny M; Laforge, Ralph; O'Toole, Michael F; Scott, Ronald D; Underberg, James A; Valuck, Thomas B; Willard, Kaye-Eileen; Ziajka, Paul E; Ito, Matthew K

    2013-01-01

    The workshop discussions focused on how low-density lipoprotein cholesterol (LDL-C) goal attainment can be enhanced with the use of health information technology (HIT) in different clinical settings. A gap is acknowledged in LDL-C goal attainment, but because of the passage of the American Recovery & Reinvestment Act and the Health Information Technology for Economic and Clinical Health Acts there is now reason for optimism that this gap can be narrowed. For HIT to be effectively used to achieve treatment goals, it must be implemented in a setting in which the health care team is fully committed to achieving these goals. Implementation of HIT alone has not resulted in reducing the gap. It is critical to build an effective management strategy into the HIT platform without increasing the overall work/time burden on staff. By enhancing communication between the health care team and the patient, more timely adjustments to treatment plans can be made with greater opportunity for LDL-C goal attainment and improved efficiency in the long run. Patients would be encouraged to take a more active role. Support tools are available. The National Lipid Association has developed a toolkit designed to improve patient compliance and could be modified for use in an HIT system. The importance of a collaborative approach between nongovernmental organizations such as the National Lipid Association, National Quality Forum, HIT partners, and other members of the health care industry offers the best opportunity for long-term success and the real possibility that such efforts could be applied to other chronic conditions, for example, diabetes and hypertension. Copyright © 2013 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  17. Low HDL cholesterol is correlated to the acute ischemic stroke with diabetes mellitus.

    Science.gov (United States)

    Luo, Yun; Li, Jingwei; Zhang, Junfeng; Xu, Yun

    2014-11-14

    To clarify the role of lipid composition in the occurrence of acute ischemic stroke (AIS) with diabetes mellitus (DM) and its influence factors. Data was collected from the patients hospitalization in Affiliated Drum Tower Hospital of Nanjing University Medical School from October 2008 to May 2012, which included AIS and non-AIS consist of transient ischemic attack (TIA) and Vertigo or dizzy. Lipid and other risk factors including blood glucose (BG), uric acid (UA), hypertension, DM and atrial fibrillation (AF) were investigated in relation to occurrence of AIS. The level of high density lipoprotein (HDL) cholesterol was decreased obviously in the DM group compared to the non-DM group and low level of HDL cholesterol was prevalent in the AIS patients with DM. logistic regression demonstrated that decreased HDL cholesterol was correlated to the AIS with DM, not all AIS, and the relative risk of ischemic stroke in low HDL cholesterol level group was 2.113 (95% CI = 1.191-3.749, P = 0.011) compared to the high level group. Furthermore, age has the obviously impact on it. HDL cholesterol was correlated to the AIS with DM just in the populations of aged ≦70 years (OR = 0.192, P = 0.000), low level of HDL cholesterol had more high risk of ischemic stroke than that in the high level group (OR = 6.818, P = 0.002). Decreased HDL cholesterol was correlated to the occurrence of AIS with DM, especially in the populations of aged ≦70 years.

  18. Lysosomes are involved in induction of steroidogenic acute regulatory protein (StAR) gene expression and progesterone synthesis through low-density lipoprotein in cultured bovine granulosa cells.

    Science.gov (United States)

    Zhang, Jin-You; Wu, Yi; Zhao, Shuan; Liu, Zhen-Xing; Zeng, Shen-Ming; Zhang, Gui-Xue

    2015-09-15

    Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The steroidogenic acute regulatory protein (StAR) is an indispensable component for transporting cholesterol to the inner mitochondrial membrane, which is one of the rate-limiting steps for progesterone synthesis. Low-density lipoprotein (LDL) supplies cholesterol precursors for progesterone formation, and the lysosomal degradation pathway of LDL is essential for progesterone biosynthesis in granulosa cells after ovulation. However, it is currently unknown how LDL and lysosomes coordinate the expression of the StAR gene and progesterone production in bovine granulosa cells. Here, we investigated the role of lysosomes in LDL-treated bovine granulosa cells. Our results reported that LDL induced expression of StAR messenger RNA and protein as well as expression of cholesterol side-chain cleavage cytochrome P-450 (CYP11A1) messenger RNA and progesterone production in cultured bovine granulosa cells. The number of lysosomes in the granulosa cells was also significantly increased by LDL; whereas the lysosomal inhibitor, chloroquine, strikingly abolished these LDL-induced effects. Our results indicate that LDL promotes StAR expression, synthesis of progesterone, and formation of lysosomes in bovine granulosa cells, and lysosomes participate in the process by releasing free cholesterol from hydrolyzed LDL. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Association of polymorphisms in genes involved in lipoprotein metabolism with plasma concentrations of remnant lipoproteins and HDL subpopulations before and after hormone therapy in postmenopausal women

    Science.gov (United States)

    Diabetes mellitus is a major risk factor for coronary heart disease (CHD), renal failure, retinopathy, and neuropathy. Lowering glycosylated hemoglobin (HbA1c) as well as low-density lipoprotein-cholesterol (LDL-C) has been associated with a decreased risk of these complications. We evaluated the ut...

  20. High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Philip J. Barter

    2013-09-01

    Full Text Available High density lipoproteins (HDLs have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic β cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

  1. Flow-cytometric determination of high-density-lipoprotein binding sites on human leukocytes

    International Nuclear Information System (INIS)

    Schmitz, G.; Wulf, G.; Bruening, T.A.; Assmann, G.

    1987-01-01

    In this method, leukocytes were isolated from 6 mL of EDTA-blood by density-gradient centrifugation and subsequently incubated with rhodamine isothiocyanate (RITC)-conjugated high-density lipoproteins (HDL). The receptor-bound conjugate particles were determined by fluorescent flow cytometry and compared with 125 I-labeled HDL binding data for the same cells. Human granulocytes express the highest number of HDL binding sites (9.4 x 10(4)/cell), followed by monocytes (7.3 x 10(4)/cell) and lymphocytes (4.0 x 10(4)/cell). Compared with conventional analysis of binding of 125 I-labeled HDL in tissue-culture dishes, the present determination revealed significantly lower values for nonspecific binding. In competition studies, the conjugate competes for the same binding sites as 125 I-labeled HDL. With the use of tetranitromethane-treated HDL3, which fails to compete for the HDL receptor sites while nonspecific binding is not affected, we could clearly distinguish between 37 degrees C surface binding and specific 37 degrees C uptake of RITC-HDL3, confirming that the HDL receptor leads bound HDL particles into an intracellular pathway rather than acting as a docking type of receptor. Patients with familial dysbetalipoproteinemia showed a significantly higher number of HDL binding sites in the granulocyte population but normal in lymphocytes and monocytes, indicating increased uptake of cholesterol-containing lipoproteins. In patients with familial hypercholesterolemia, HDL binding was increased in all three cell types, indicating increased cholesterol uptake and increased cholesterol synthesis. The present method allows rapid determination of HDL binding sites in leukocytes from patients with various forms of hyper- and dyslipoproteinemias

  2. Trans-intestinal cholesterol efflux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, Carlos L. J.; Ottenhoff, Roelof; van den Oever, Karin; de Waart, Dirk R.; Kruyt, J. Kar; Zhao, Ying; van Berkel, Theo J. C.; Havekes, Louis M.; Aerts, Johannes M.; van Eck, Miranda; Rensen, Patrick C. N.; Groen, Albert K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding

  3. Small high-density lipoprotein (HDL) subclasses are increased with decreased activity of HDL-associated phospholipase A₂ in subjects with prediabetes.

    Science.gov (United States)

    Filippatos, Theodosios D; Rizos, Evangelos C; Tsimihodimos, Vasilios; Gazi, Irene F; Tselepis, Alexandros D; Elisaf, Moses S

    2013-06-01

    Alterations in high-density lipoprotein (HDL) subclass distribution, as well as in the activities of HDL-associated enzymes, have been associated with increased cardiovascular disease (CVD) risk. HDL subclass distribution and the activities of HDL-associated enzymes remain unknown in prediabetic patients, a condition also associated with increased CVD risk. The aim of the present study was to assess any differences in HDL subclass distribution (using polyacrylamide gel electrophoresis) and in activities of HDL-associated enzymes between prediabetic (impaired fasting glucose, IFG, n = 80) and non-prediabetic subjects (n = 105). Subjects with prediabetes had significantly increased waist circumference, blood pressure and triacylglycerol (TAG) levels compared with subjects with fasting glucose levels prediabetic subjects compared with their controls (p prediabetes (p prediabetes. In a stepwise linear regression analysis, the proportion of small HDL3 over HDL-C concentration was independently associated with the presence of prediabetes and with total cholesterol and TAG concentration (positively), as well as with HDL-C levels (negatively). We also observed a trend of increased small dense low-density lipoprotein cholesterol levels in prediabetic subjects compared with their controls. Subjects with IFG exhibit increased proportion of small HDL3 particles combined with decreased activity of the anti-atherogenic HDL-LpPLA₂.

  4. Low-density lipoprotein modified by myeloperoxidase oxidants induces endothelial dysfunction

    DEFF Research Database (Denmark)

    Abdo, Adrian; Rayner, B.S.; van Reyk, D.M.

    2017-01-01

    Low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) is present in atherosclerotic lesions, where it is implicated in the propagation of inflammation and acceleration of lesion development by multiple pathways, including the induction of endothelial......, although emerging evidence suggests that these particles have distinct biological properties. This is important because elevated plasma SCN- is linked with both the propagation and prevention of atherosclerosis. In this study, we demonstrate that both HOSCN- and HOCl-modified LDL inhibit endothelium......-mediated vasorelaxation ex vivo in rat aortic ring segments. In vitro experiments with human coronary artery endothelial cells show that HOSCN-modified LDL decreases in the production of nitric oxide (NO•) and induces the loss of endothelial nitric oxide synthase (eNOS) activity. This occurs to a similar extent...

  5. Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein

    Science.gov (United States)

    Arai, Hirofumi; Berlett, Barbara S.; Chock, P. Boon; Stadtman, Earl R.

    2005-07-01

    Oxidation of low-density lipoprotein (LDL) may play an important role in atherosclerosis. We studied the effects of bicarbonate/CO2 and phosphate buffer systems on metal ion-catalyzed oxidation of LDL to malondialdehyde (MDA) and to protein carbonyl and MetO derivatives. Our results revealed that LDL oxidation in mixtures containing free iron or heme derivatives was much greater in bicarbonate/CO2 compared with phosphate buffer. However, when copper was substituted for iron in these mixtures, the rate of LDL oxidation in both buffers was similar. Iron-catalyzed oxidation of LDL was highly sensitive to inhibition by phosphate. Presence of 0.3-0.5 mM phosphate, characteristic of human serum, led to 30-40% inhibition of LDL oxidation in bicarbonate/CO2 buffer. Iron-catalyzed oxidation of LDL to MDA in phosphate buffer was inhibited by increasing concentrations of albumin (10-200 μM), whereas MDA formation in bicarbonate/CO2 buffer was stimulated by 10-50 μM albumin but inhibited by higher concentrations. However, albumin stimulated the oxidation of LDL proteins to carbonyl derivatives at all concentrations examined in both buffers. Conversion of LDL to MDA in bicarbonate/CO2 buffer was greatly stimulated by ADP, ATP, and EDTA but only when EDTA was added at a concentration equal to that of iron. At higher than stoichiometric concentrations, EDTA prevented oxidation of LDL. Results of these studies suggest that interactions between bicarbonate and iron or heme derivatives leads to complexes with redox potentials that favor the generation of reactive oxygen species and/or to the generation of highly reactive CO2 anion or bicarbonate radical that facilitates LDL oxidation. Freely available online through the PNAS open access option.Abbreviations: LDL, low-density lipoprotein; MDA, malondialdehyde; MetO, methionine sulfoxide.

  6. LDL cholesterol in CKD-to treat or not to treat?

    NARCIS (Netherlands)

    Massy, Ziad A.; de Zeeuw, Dick

    In the majority of patients with chronic kidney disease (CKD) the total and low-density lipoprotein (LDL) cholesterol are usually normal, with the exception of patients with nephrotic-range proteinuria and in peritoneal dialysis patients. Moreover, epidemiological evidence shows that the link

  7. Moderate alcohol consumption and changes in postprandial lipoproteins of premenopausal and postmenopausal women: a diet-controlled, randomized intervention study.

    Science.gov (United States)

    van der Gaag, M S; Sierksma, A; Schaafsma, G; van Tol, A; Geelhoed-Mieras, T; Bakker, M; Hendriks, H F

    2000-01-01

    Moderate alcohol consumption is associated with a reduced risk of coronary heart disease. Earlier studies in men have shown that moderate alcohol consumption affects lipoprotein metabolism and hemostasis. In this diet-controlled, randomized, crossover trial, we investigated the effect on lipoprotein metabolism of moderate consumption of red wine or red grape juice with evening dinner for 3 weeks in premenopausal women using oral contraceptives and in postmenopausal women. After 3 weeks, blood samples were collected 1 hour before dinner up to 19 hours after starting dinner at 2-hour or 4-hour intervals. Plasma triglyceride concentrations and very low density lipoprotein (VLDL) triglyceride levels peaked 3 hours after dinner with wine in both premenopausal and postmenopausal women. After wine consumption, the overall high-density lipoprotein (HDL) cholesterol level was increased in postmenopausal women (mean increase 0.17 mmol/L, or 12%, p = 0.03), and the plasma low-density lipoprotein (LDL) cholesterol level was reduced in premenopausal women (mean reduction 0.35 mmol/L, or 12%, p = 0.01) as compared with grape juice consumption. The findings suggest that postprandial lipoprotein metabolism after moderate alcohol consumption differs between oral contraceptive-using premenopausal women and postmenopausal women. The response of postmenopausal women to alcohol resembled the response found in earlier studies in men.

  8. Effects of plant sterols and olive oil phenols on serum lipoproteins in humans

    NARCIS (Netherlands)

    Vissers, M.N.

    2001-01-01

    The studies described in this thesis investigated whether minor components from vegetable oils can improve health by decreasing cholesterol concentrations or oxidative modification of low-density-lipoprotein (LDL) particles.

    The plant sterolsβ-sitosterol and sitostanol are

  9. Cholesterol pathways affected by small molecules that decrease sterol levels in Niemann-Pick type C mutant cells.

    Directory of Open Access Journals (Sweden)

    Madalina Rujoi

    2010-09-01

    Full Text Available Niemann-Pick type C (NPC disease is a genetically inherited multi-lipid storage disorder with impaired efflux of cholesterol from lysosomal storage organelles.The effect of screen-selected cholesterol lowering compounds on the major sterol pathways was studied in CT60 mutant CHO cells lacking NPC1 protein. Each of the selected chemicals decreases cholesterol in the lysosomal storage organelles of NPC1 mutant cells through one or more of the following mechanisms: increased cholesterol efflux from the cell, decreased uptake of low-density lipoproteins, and/or increased levels of cholesteryl esters. Several chemicals promote efflux of cholesterol to extracellular acceptors in both non-NPC and NPC1 mutant cells. The uptake of low-density lipoprotein-derived cholesterol is inhibited by some of the studied compounds.Results herein provide the information for prioritized further studies in identifying molecular targets of the chemicals. This approach proved successful in the identification of seven chemicals as novel inhibitors of lysosomal acid lipase (Rosenbaum et al, Biochim. Biophys. Acta. 2009, 1791:1155-1165.

  10. Structure-function relationships in reconstituted HDL: Focus on antioxidative activity and cholesterol efflux capacity.

    Science.gov (United States)

    Cukier, Alexandre M O; Therond, Patrice; Didichenko, Svetlana A; Guillas, Isabelle; Chapman, M John; Wright, Samuel D; Kontush, Anatol

    2017-09-01

    High-density lipoprotein (HDL) contains multiple components that endow it with biological activities. Apolipoprotein A-I (apoA-I) and surface phospholipids contribute to these activities; however, structure-function relationships in HDL particles remain incompletely characterised. Reconstituted HDLs (rHDLs) were prepared from apoA-I and soy phosphatidylcholine (PC) at molar ratios of 1:50, 1:100 and 1:150. Oxidative status of apoA-I was varied using controlled oxidation of Met112 residue. HDL-mediated inactivation of PC hydroperoxides (PCOOH) derived from mildly pre-oxidized low-density lipoprotein (LDL) was evaluated by HPLC with chemiluminescent detection in HDL+LDL mixtures and re-isolated LDL. Cellular cholesterol efflux was characterised in RAW264.7 macrophages. rHDL inactivated LDL-derived PCOOH in a dose- and time-dependent manner. The capacity of rHDL to both inactivate PCOOH and efflux cholesterol via ATP-binding cassette transporter A1 (ABCA1) increased with increasing apoA-I/PC ratio proportionally to the apoA-I content in rHDL. Controlled oxidation of apoA-I Met112 gradually decreased PCOOH-inactivating capacity of rHDL but increased ABCA1-mediated cellular cholesterol efflux. Increasing apoA-I content in rHDL enhanced its antioxidative activity towards oxidized LDL and cholesterol efflux capacity via ABCA1, whereas oxidation of apoA-I Met112 decreased the antioxidative activity but increased the cholesterol efflux. These findings provide important considerations in the design of future HDL therapeutics. Non-standard abbreviations and acronyms: AAPH, 2,2'-azobis(-amidinopropane) dihydrochloride; ABCA1, ATP-binding cassette transporter A1; apoA-I, apolipoprotein A-I; BHT, butylated hydroxytoluene; CV, cardiovascular; EDTA, ethylenediaminetetraacetic acid; HDL-C, high-density lipoprotein cholesterol; LOOH, lipid hydroperoxides; Met(O), methionine sulfoxide; Met112, methionine 112 residue; Met86, methionine 86 residue; oxLDL, oxidized low-density

  11. EFFECTS OF EXERCISE TRAINING ON BLOOD LIPIDS AND LIPOPROTEINS IN CHILDREN AND ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    Kerstin Stoedefalke

    2007-09-01

    Full Text Available The following review aims to describe what is known about the effects of exercise training in children and adolescents on the following blood lipids and lipoproteins: total cholesterol (TC, high density lipoprotein cholesterol (HDL-C, low density lipoprotein cholesterol (LDL-C, and triglycerides (TG. Only studies that described mode, frequency, duration and intensity of the exercise were included in the review. The results of the studies reviewed were equivocal. Clearly the effects of exercise training on the blood lipid and lipoprotein levels of normolipidemic children and adolescents are equivocal. Of the 14 studies reviewed, six observed a positive alteration in the blood lipid and lipoprotein profile, four of the studies observed no alteration in the blood lipid and lipoprotein profile and one study observed a negative effect on HDL-C but an overall improvement in the lipid and lipoprotein profile due to the decrease in the TC/HDL ratio. It appears that methodological problems present in the majority of the exercise training studies limits the ability to make a conclusive, evidence based statement regarding the effect exercise training has on blood lipid levels in normolipidemic children. Most of the research design flaws can be linked to one or more of the following: small numbers of subjects in each study, low or no representation of girls, inclusion of both boys and girls in the subject pool, inclusion of boys and girls at different maturational stages in the subject pool, exercise training regimes that do not adequately control for exercise intensity, exercise training regimes that do not last longer than 8 weeks and exercise training studies that do not have an adequate exercise volume to elicit a change. Ideally, future research should focus on longitudinal studies which examine the effects of exercise training from the primary school years through adulthood

  12. Blood lipid concentrations and lipoprotein patterns in captive and wild American black bears (Ursus americanus).

    Science.gov (United States)

    Frank, Nicholas; Elliott, Sarah B; Allin, Shawn B; Ramsay, Edward C

    2006-02-01

    To compare blood lipid concentrations and lipoprotein patterns for captive and wild American black bears (Ursus americanus). 7 captive and 9 wild adult (> or = 4 years old) black bears. Blood was collected from 2 groups of captive black bears (groups A and B) and 1 group of wild black bears (group C). Blood triglyceride (TG) and cholesterol concentrations were compared among groups. Plasma lipoproteins were isolated by use of a self-generating gradient of iodixanol, and lipoprotein patterns were compared between groups A and B. Captive bears (mean +/- SD, 187.8 +/- 44.4 kg) weighed significantly more than wild bears (mean, 104.8 +/- 41.4 kg), but mean body weight did not differ between groups A and B. Mean blood TG concentrations for groups B (216.8 +/- 16.0 mg/dL) and C (190.7 +/- 34.0 mg/dL) were significantly higher than that of group A (103.9 +/- 25.3 mg/dL). Mean blood cholesterol concentration was also significantly higher for group B (227.8 +/- 8.2 mg/dL) than for groups A (171.7 +/- 35.5 mg/dL) or C (190.8 +/- 26.8 mg/dL). Mean very-low-density lipoprotein TG and low-density lipoprotein cholesterol concentrations were 2- and 3-fold higher, respectively, for group B, compared with concentrations for group A. Blood lipid concentrations vary significantly among populations of black bears. Plasma lipoprotein patterns of captive bears differed significantly between colonies and may have reflected differences in diet or management practices.

  13. EFFECT OF DIETARY OLIVE OIL/CHOLESTEROL ON SERUM LIPOPROTEINS, LIPID PEROXIDATION, AND ATHEROSCLEROSIS IN RABBITS

    Directory of Open Access Journals (Sweden)

    R MAHDAVI

    2003-03-01

    Full Text Available Introduction: High plasma cholesterol levels, mainly LDL are a widely recognized major risk factor for Coronary Heart Disease (CHD. According to the epidemiologic studies findings, people from the Mediterranean countries, have lower CHD rats than other countries, in these countries usual diet is high in olive oil. The present study compares the effects of cholesterol enriched diet with or without adding olive oil on serum Lipoproteins, lipid per oxidation, and atherosclerosis development. Method: Twenty Dutch male rabbits were Categorized to four groups (one group as Control, and others as Experimental. They received one of standard, cholesterol - rich, olive oil rich and combined (cholesterol + olive oil diet for Twelve weeks. Fasting blood samples from heart were collected at the beginning, and the end of Experimental period. Means of total cholesterol, HDL-Ctriglycerides, MDA and antioxidant caperimental period, significant differences were showed in total cholesterol, HDL-C, triglyceride and MDA between groups. Results: The comparison of cholesterol rich diet with cholesterol + olive oil showed a higher mean of MDA in cholesterol rich group (P < 0.001. Biochemical factors and aortic lesion degree showed no significant difference between standard and olive oil group. Aortic lesions in cholesterol + olive oil showed nonsignificant lower degree than cholesterol group. Discussion: This findings showed preventive effect of olive oil against atherosclerosis which is independent of plasma lipoprotein effect, and suggested that probably olive oil acts on arteries directly.

  14. In vitro studies of PBT Nonwoven Fabrics adsorbent for the removal of low density lipoprotein from hyperlipemia plasma

    Energy Technology Data Exchange (ETDEWEB)

    Cao Ye; Wang Hong [Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052 (China); Yang Chao [State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240 (China); Zhong Rui [Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052 (China); Lei Yu [Chengdu Blood Center, Chengdu 610041 (China); Sun Kang [State Key Lab of Metal Matrix Composites, Shanghai Jiao Tong University, Shanghai 200240 (China); Liu Jiaxin, E-mail: jxliu8122@vip.sina.com [Institute of Blood Transfusion, Chinese Academy of Medical Sciences and Peking Union Medical College, Chengdu 610052 (China)

    2011-06-15

    Polyanion ligands such as acrylic acid (AA) and heparin were grafted on PBT Nonwoven Fabrics (PBTNF) to study their effect on the adsorption of low density lipoprotein (LDL). These modified PBTNFs were characterized by Horizontal Attenuated Total Reflectance Fourier Transform Infrared spectroscopy and X-ray Photoelectron spectroscopy. The blood compatibilities of the modified PBTNFs were examined using in vitro hemolysis rate (HR), platelet adhesion, total protein (TP) and activated partial thromboplastin time. The results showed that direct immobilized heparin could improve PBTNF-PAA's blood compatibility and decrease the adsorption capability of useful high density lipoprotein, but would possess so low bioactivity that could not further improve the absorption of LDL and TC. Since the PBTNF-PAA55-Heparin adsorbent had quite good adsorption selectivity for these proteins, it can be an excellent candidate for depletion of LDL with good blood compatibility.

  15. The affection of the disturbance of the hydrodynamics of blood in case of stress on pathological increase of level of low density lipoproteins in blood. The formation of cylindrical plaques, and their participation in the development of acute ischemic disorders of heart and brain.

    Science.gov (United States)

    Rusanov, S E

    2017-09-01

    In this article is given the new insight about the affection of stress on the increase of level of low density lipoproteins (LDL) in the blood, which is connected with the disturbance of hydrodynamics in the bloodstream, the attention was paid to the cylindrical cholesterol plaque, and it's classification. The disturbance of hydrodynamics of blood under the stress leads to the formation of a cylindrical cholesterol plaque, which repeats the contour of the vessel, and leads to the ischemic disorders of the heart and brain. The cylindrical cholesterol plaque goes through several stages of development: friable, yielding, dense, old. In the case of destruction of friable, fresh cholesterol plaque, releases a big quantity of low-density lipoproteins. This leads to the pathological increase of level of LDL in the blood. In the case of long disturbance of hydrodynamics, occurs the formation of strong links between low-density lipoproteins. Yielding cholesterol plaque is formed. Further maturation of cylindrical cholesterol plaque, leads to it's densifying and damage. We may emphasize, that short periods of strong contraction and expansion of vessels lead to the increase of level of LDL in the blood. Self-dependent restoration of normal level of LDL in blood occurs in the case of restoration of pressure in the limits of numbers, which are specific for particular person, and which don't exceed the physiological standard. Among patients with long duration of stress, the duration of vasospasm increases. LDL, without having a possibility to crumble, begin to stick together and form the yielding cylindrical plaque. It is characterized by having of not so strong connection with the vascular wall, and maintains only at the expanse of iteration of the vascular wall, it has cylindrical shape, is elastic and yellow. The thickness and length of walls depends on the degree of cross-clamping during the time of formation of yielding cylindrical plaque. In the case of stopping of spasm

  16. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    Energy Technology Data Exchange (ETDEWEB)

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  17. Lecithin Cholesterol Acyltransferase: An Anti- or Pro-atherogenic Factor?

    OpenAIRE

    Rousset, Xavier; Shamburek, Robert; Vaisman, Boris; Amar, Marcelo; Remaley, Alan T.

    2011-01-01

    Lecithin cholesterol acyl transferase (LCAT) is a plasma enzyme that esterifies cholesterol and raises high-density lipoprotein cholesterol, but its role in atherosclerosis is not clearly established. Studies of various animal models have yielded conflicting results, but studies done in rabbits and non-human primates, which more closely simulate human lipoprotein metabolism, indicate that LCAT is likely atheroprotective. Although suggestive, there are also no biomarker studies that mechanisti...

  18. Degradation of high density lipoprotein in cultured rat luteal cells

    International Nuclear Information System (INIS)

    Rajan, V.P.; Menon, K.M.J.

    1986-01-01

    In rat ovary luteal cells, degradation of high density lipoprotein (HDL) to tricholoracetic acid (TCA)-soluble products accounts for only a fraction of the HDL-derived cholesterol used for steroidogenesis. In this study the authors have investigated the fate of 125 I]HDL bound to cultured luteal cells using pulse-chase technique. Luteal cell cultures were pulse labeled with [ 125 I]HDL 3 and reincubated in the absence of HDL. By 24 h about 50% of the initallay bound radioactivity was released into the medium, of which 60-65% could be precipitated with 10% TCA. Gel filtration of the chase incubation medium on 10% agarose showed that the amount of TCA-soluble radioactivity was nearly completely accounted for by a sharp peak in the low molecular weight region which was identified as 96% monoiodotyrosine by paper chromatography. The TCA-precipitable radioactivity was nearly completely accounted for by a sharp peak in the low molecular weight region which was identified as 96% monoiodotyrosine by paper chromatography. The TCA-precipitable radioactivity eluted over a wide range of molecular weights (15,000-80,000), and there was very little intact HDL present. Electrophoresis of the chase medium showed that component of the TCA-precipitable portion had mobility similar to apo AI. Lysosomal inhibitors of receptor-mediated endocytosis had no effect on the composition or quantity of radioactivity released during chase incubation. The results show that HDL 3 binding to luteal cells is followed by complete degradation of the lipoprotein, although the TCA-soluble part does not reflect the extent of degradation

  19. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease

    DEFF Research Database (Denmark)

    Wittrup, Hans H; Andersen, Rolf V; Tybjaerg-Hansen, Anne

    2006-01-01

    Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD).......Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD)....

  20. Synthetic Nano-Low Density Lipoprotein as Targeted Drug DeliveryVehicle for Glioblastoma Multiforme

    Energy Technology Data Exchange (ETDEWEB)

    Nikanjam, Mina; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Shu,Xiao; Budinger, Thomas F.; Forte, Trudy M.

    2006-06-14

    This paper discribes a synthetic low density lipoprotein(LDL) made by complexing a 29 amino acid that consists of a lipid bindingdomain and the LDL receptor binding domain with a lipid microemulsion.The nano-LDL particles were intermdiate in size between LDL and HDL andbound to LDL receptors on GBM brain tumor cells. Synthetic nano-LDLuptake by GBM cells was LDL receptor specific and dependent on cellreceptor number. It is suggested that these synthetic particles can serveas a delivery vehicle for hydophobic anti-tumor drugs by targeting theLDL receptor.

  1. Homozygous Familial Hypercholesterolemia Patients With Identical Mutations Variably Express the LDLR (Low-Density Lipoprotein Receptor): Implications for the Efficacy of Evolocumab.

    Science.gov (United States)

    Thedrez, Aurélie; Blom, Dirk J; Ramin-Mangata, Stéphane; Blanchard, Valentin; Croyal, Mikaël; Chemello, Kévin; Nativel, Brice; Pichelin, Matthieu; Cariou, Bertrand; Bourane, Steeve; Tang, Lihua; Farnier, Michel; Raal, Frederick J; Lambert, Gilles

    2018-03-01

    Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial (Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders). Ten patients were true homozygotes (FH1/FH1) and 5 identical compound heterozygotes (FH1/FH2). Lymphocytes were plated with or without mevastatin, recombinant PCSK9 (rPCSK9), or a PCSK9-neutralizing antibody. Cell surface LDLR expression was analyzed by flow cytometry. All HoFH lymphocytes had reduced cell surface LDLR expression compared with non-FH lymphocytes, for each treatment modality. Lymphocytes from FH1/FH2 patients (LDLR defective/negative) displayed the lowest LDLR expression levels followed by lymphocytes from FH1/FH1 patients (defective/defective). Mevastatin increased, whereas rPCSK9 reduced LDLR expression. The PCSK9-neutralizing antibody restored LDLR expression. Lymphocytes displaying higher LDLR expression levels were those isolated from patients presenting with lowest levels of LDL-C and apolipoprotein B, before and after 24 weeks of evolocumab treatment. These negative correlations remained significant in FH1/FH1 patients and appeared more pronounced when patients with apolipoprotein E3/E3 genotypes were analyzed separately. Significant positive correlations were found between the levels of LDLR expression and the percentage reduction in LDL-C on evolocumab treatment. Residual LDLR expression in HoFH is a major determinant of LDL-C levels and seems to drive their individual response to evolocumab. © 2017 American Heart Association

  2. Thermodynamics of the interaction between bovine binder of sperm BSP1 and low-density lipoprotein from hen's egg yolk

    Energy Technology Data Exchange (ETDEWEB)

    Lusignan, Marie-France; Manjunath, Puttaswamy [Maisonneuve-Rosemont Hospital Research Center and Department of Medicine, Universite de Montreal, C.P. 6128, Succ. Centre Ville, Montreal, Quebec, Canada H3C 3J7 (Canada); Lafleur, Michel, E-mail: michel.lafleur@umontreal.ca [Department of Chemistry, Centre for Self-Assembled Chemical Structures (CSACS), Universite de Montreal, C.P. 6128, Succ. Centre Ville, Montreal, Quebec, Canada H3C 3J7 (Canada)

    2011-03-20

    Research highlights: {yields} Isothermal titration calorimetry revealed Binder-of-SPerm BSP1 protein has high affinity for egg yolk low density lipoproteins. {yields} It is estimated that 104 BSP1 molecules could bind one LDL particle. {yields} BSP1 has 2 phosphocholine binding sites and the BSP1/LDL ratio corresponds to 1.6 phosphatidylcholine per bound BSP1. {yields} The strong interaction between LDL particles and BSP1 is proposed to be important for sperm protection by egg yolk extender. - Abstract: Egg yolk is used in extender to protect sperm from cold shock and freezing during preservation. It is the low-density lipoprotein (LDL) fraction of egg yolk that protects sperm. Even though essential for sperm capacitation, the major proteins from bull seminal plasma, the Binder of SPerm (BSP) proteins, are detrimental for sperm preservation because they induce a continual phospholipids and cholesterol efflux from sperm membranes. The BSP proteins were proposed to bind to egg yolk LDL, preventing the sperm membrane damage. We characterized the binding between the BSP proteins and the LDL by isothermal titration calorimetry, providing the thermodynamics and quantitative description of this putative association. The association between BSP1 (major BSP proteins) and LDL is characterized by an affinity constant (K{sub a}) of 3.4 {+-} 0.4 {mu}M{sup -1}. A protein/LDL ratio of 104 {+-} 5 was determined indicating that 104 molecules of BSP1 would bind to one LDL particle. This stoichiometry leads to proposing that the association involves 1.6 {+-} 0.1 phosphatidylcholines (PC) per BSP protein. This finding is satisfactorily consistent with the fact that each BSP1 protein has 2 binding sites for choline group. In conclusion, the formation of a high affinity complex between BSP1 and LDL is proposed to be important for the protection of sperm by egg yolk extender.

  3. Metabolism of (125I)tyramine cellobiose-labeled low density lipoproteins in squirrel monkeys

    International Nuclear Information System (INIS)

    Portman, O.W.; Alexander, Manfred

    1985-01-01

    Low density lipoproteins labeled with ( 125 I)tyramine cellobiose (( 125 I)TC-LDL) were removed from the circulation of squirrel monkeys at a similar but slightly slower rate than LDLs labeled with 125 I, ( 125 I)hydroxypenyl propionic acid, or ( 3 H)leucine. After the simultaneous injection of (( 125 I)TC-LDL) and ( 131 I)LDL labeled with 131 ICI, the 125 I was also removed at a slightly slower rate than 131 I. Most of the radioactivity was retained in tissues and not excreted during the 24 h after injection of ( 125 I)TC-LDL. This finding supports the claim of Pittman et al. (18) that ( 125 I)TC-LDL can be used to determine the irreversible uptake of LDL by different tissues. The liver cleared more LDL than any other organ, but the adrenals and ovaries were more active per gram. Trichloroacetic acid (TCA) precipitated more than 80% of the radioactivity in the tissues that had low 125 I uptake, but only about 50% of the 125 I in more active tissues (liver, adrenals, ovaries and spleen). Only a small percentage of 125 I in urine and bile was TCA-precipitable. In the dual label experiment with ( 125 I)TC-LDL and ( 131 I)LDL there was a selective retention of 125 I in samples from liver, spleen, adrenals, and perhaps testes, and an almost complete selectivity for 125 I in bile and feces. The aortic intima plus inner media (AIM) cleared much less LDL than other tissues, but the uptake by the entire AIM was proportional to the cholesterol concentration and weight of the total AIM. There was, however, no correlation between either of the latter two measurements and the uptake of LDL per pram of AIM. (author)

  4. Low-density lipoprotein as a potential vehicle for chemotherapeutic agents and radionucleotides in the management of gynecologic neoplasms

    International Nuclear Information System (INIS)

    Gal, D.; Ohashi, M.; MacDonald, P.C.; Buchsbaum, H.J.; Simpson, E.R.

    1981-01-01

    Cholesterol metabolism was studied in cells from two established gynecologic cancer cell lines which were maintained in monolayer cultures. The cell lines were derived and established from poorly differentiated epidermoid cervical carcinoma (EC-50) and endometrial adenocarcinoma (AC-258). The specific activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting enzyme of cholesterol de novo synthesis, in AC-258 cells (1700 pmoles x mg-1 microsomal protein x min-1) was three times higher than that found in EC-50 cells (550 pmoles x mg-1 microsomal protein x min-1). However, epidermoid cervical cancer cells (EC-50) metabolized low-density lipoprotein (LDL), the major transport vehicle for cholesterol in plasma, at a very high rate (14,000 ng x mg-1 cell protein x 6 hours). This rate is fifteen times greater than the rate observed in fetal adrenal tissue and fifty times greater than the rate observed in nonneoplastic gynecologic tissue, each in organ culture. Both cancer cells (EC-50 and AC-258) in monolayer culture were shown to have specific receptors for LDL. These cancer cells demonstrate no defect in LDL metabolism, and lysosomal degradation of LDL was blocked by chloroquine. From the results of studies of specific binding of LDL in tissues obtained from nude mice it was demonstrated that membrane fractions prepared from EC-50 cells, after propagation in the mice, contained fifteen to thirty times more specific binding capacity for [125I]iodo-LDL than vital organs of the mouse, such as the liver, heart, lung, kidney, or brain. The results of these studies are suggestive that certain tumor cells might have a higher affinity for LDL than normal tissues and cytotoxic drugs or radionucleotides ligated to the LDL macromolecule may be utilized for the specific delivery of these agents

  5. Effects of peach palm oil on performance, serum lipoproteins and haemostasis in broilers.

    Science.gov (United States)

    Baldizán, G; Oviedo, M; Michelangeli, C; Vargas, R E

    2010-12-01

    1. An experiment was conducted to study the comparative effects of peach palm oil (PPO, Bactris gasipaes H.B.K), crude palm oil (CPO, Elaeis guinenesis), maize oil (MO) and beef tallow (BT) on serum total and lipoprotein cholesterol levels and haemostatic factors in broiler chickens. 2. Four experimental diets were formulated to be isocaloric (14·2 MJ AME(N)/kg) and isonitrogenous (230 g CP/kg). PPO was extracted from the whole dry fruit with hexane. Each fat was added to the diet in an amount equivalent to 25% of total dietary calories. Six replicate groups of eight male broiler chicks were assigned randomly to each dietary treatment. Diets were fed on ad libitum basis. The experiment lasted 42 d. 3. At 42 d, birds were fasted overnight and three chickens/dietary treatment were utilised to draw blood for lipoprotein separation. Various haemostatic factors were determined in thrombocyte-poor plasma. Thrombocyte aggregation was assayed in whole blood. 4. No significant differences were detected in body-weight gain or feed efficiency between the chickens fed on the PPO diet and those receiving the CPO, MO or BT diets. Total serum cholesterol (TC), very low density lipoprotein cholesterol and low density lipoprotein cholesterol (LDL(C)) were not significantly affected after consuming the PPO, CPO and MO diets. Serum high density lipoprotein cholesterol (HDL(C)) was reduced only by the MO diet. Birds fed on the PPO diet had a significantly lower [corrected] LDLC/HDLC ratio compared with other dietary treatments 5. Thrombocyte count and thrombin time were not significantly affected by the experimental diets. Dietary oils significantly affected prothrombin time, fibrinogen concentration and thrombocyte aggregation. PPO and MO diets elicited the lowest fibrinogen levels compared to the CPO and BT diets. Thrombocyte aggregation in broilers fed on the PPO diet was similar to that of the CPO, MO and BT diets. 6. The results suggest that PPO might efficiently provide up to

  6. Structural and metabolic heterogeneity of plasma low density lipoproteins in nonhuman primates

    International Nuclear Information System (INIS)

    Marzetta, C.A.

    1986-01-01

    To test the hypothesis that a variety of precursor particles secreted by the liver could result in heterogeneity of LDL products in plasma, the metabolic fate of selected radiolabeled hepatic lipoproteins evaluated was determined in vivo. The hepatic lipoproteins evaluated were isolated from liver perfusate and were triglyceride-rich VLDL (d < 1.006 or d < 1.017) and phospholipid-rich LDL (1.017 < d < 1.049 or 1.030 < d < 1.063). Radiolabeled autologous plasma LDL were injected into recipient animals together with the radiolabeled hepatic lipoproteins. Density gradient ultracentrifugation and gel filtration were used to characterize the distribution of radiolabeled lipoproteins in the plasma at selected times after injection. A variety of hepatic lipoproteins were precursors to lipoproteins that resembled plasma LDL. Between 22 to 80% of the injected dose of radiolabeled hepatic lipoprotein apo B-100 was converted to plasma LDL-like particles, regardless of the type of hepatic lipoprotein injected. A kinetic model was generated to describe the metabolic behavior of hepatic VLDL-derived and plasma LDL-derived apo B-100 radioactivity. Both models required multiple metabolic pools to fit the data. Hepatic VLDL-derived apo B-100 radioactivity was metabolized rapidly into various kinds of LDL subfractions. This rapid conversion of hepatic VLDL apo B-100 to LDL apo B-100 may be analogous to the portion of plasma VLDL that gets converted to LDL without passing through the delipidation cascade that has been described in humans and has been termed direct LDL production

  7. Evaluation of biodistribution and imaging of atherosclerotic lesions using 111In-labeled low-density lipoprotein

    International Nuclear Information System (INIS)

    Yamashina, Hisayo

    1993-01-01

    111 In-labeled low-density lipoprotein (LDL) was administered to Watanabe heritable hyperlipidemic rabbits (WHHL group) and control rabbits (control group) to evaluate its biodistribution and scintigraphic images by γ-camera and radioactivity of each organ. With external imaging, the heart, liver, kidney, bone and spleen of each rabbit were observed. By setting the region of interest, the liver/heart ratio of the WHHL group was significantly lower than that of the control group (p 111 In-labeled-LDL was recognized in the aortic arch, bifurcation of intercostal and celiac artery in the WHHL group. By the use of labeled LDL with the combination of γ-camera, it is capable of detecting the regulation of lipoprotein metabolism and imaging atherosclerotic lesions externally. (author)

  8. Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

    Energy Technology Data Exchange (ETDEWEB)

    Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

    1991-12-01

    The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

  9. Cholesteryl ester transfer activity in plasma measured by using solid-phase-bound high-density lipoprotein

    International Nuclear Information System (INIS)

    Sparks, D.L.; Frohlich, J.; Cullis, P.; Pritchard, P.H.

    1987-01-01

    We studied the ability of lipid-transfer factors in plasma to promote transfer, to endogenous lipoproteins, of [ 3 H]cholesteryl ester from high-density lipoprotein (HDL) covalently bound to Sepharose 4B beads. After incubation for 2 h at 37 degrees C, 12 to 14% of the [ 3 H]cholesteryl ester had been transferred to the lipoproteins of the plasma, in the proportions 57% to HDL and 43% to low- and very-low-density lipoproteins. This process was a function of the amount of plasma present and was stimulated by addition of partly purified lipid-transfer protein. Transfer also depended on the concentration of donor HDL but was independent of the amount of acceptor lipoprotein. This simple evaluation of cholesteryl ester transfer does not require removal of lipoproteins from the plasma before incubation

  10. Lipoprotein Nanoplatform for Targeted Delivery of Diagnostic and Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Jerry D. Glickson

    2008-03-01

    Full Text Available Low-density lipoprotein (LDL provides a highly versatile natural nanoplatform for delivery of visible or near-infrared fluorescent optical and magnetic resonance imaging (MRI contrast agents and photodynamic therapy and chemotherapeutic agents to normal and neoplastic cells that overexpress low-density lipoprotein receptors (LDLRs. Extension to other lipoproteins ranging in diameter from about 10 nm (high-density lipoprotein [HDL] to over a micron (chylomicrons is feasible. Loading of contrast or therapeutic agents onto or into these particles has been achieved by protein loading (covalent attachment to protein side chains, surface loading (intercalation into the phospholipid monolayer, and core loading (extraction and reconstitution of the triglyceride/cholesterol ester core. Core and surface loading of LDL have been used for delivery of optical imaging agents to tumor cells in vivo and in culture. Surface loading was used for delivery of gadolinium-bis-stearylamide contrast agents for in vivo MRI detection in tumor-bearing mice. Chlorin and phthalocyanine near-infrared photodynamic therapy agents (≤ 400/LDL have been attached by core loading. Protein loading was used to reroute the LDL from its natural receptor (LDLR to folate receptors and could be used to target other receptors. A semisynthetic nanoparticle has been constructed by coating magnetite iron oxide nanoparticles with carboxylated cholesterol and overlaying a monolayer of phospholipid to which apolipoprotein A1 or E was adsorbed for targeting HDL or adsorbing synthetic amphipathic helical peptides ltargeting LDL or folate receptors. These particles can be used for in situ loading of magnetite into cells for MRI-monitored cell tracking or gene expression.

  11. Changes of very low-density lipoprotein concentration in hepatic blood from cows with fasting-induced hepatic lipidosis.

    Science.gov (United States)

    Oikawa, Shin; Mizunuma, Yuko; Iwasaki, Yukari; Tharwat, Mohamed

    2010-10-01

    The purpose of this study was to evaluate changes of very low-density lipoprotein (VLDL) components in hepatic blood (HB) from 5 nonlactating nonpregnant cows fasted from days 0 to 3 and subsequently refed to day 10 and, in addition, to assess those of other lipoproteins. Increased phospholipid concentrations in each lipoprotein after the start of fasting suggested their availability for the surface lipids of lipoproteins. Although the VLDL-triglyceride (TG) concentration in HB from all cows increased on day 1, the value on day 4 became similar to that on day 0. However, the concentration on day 10 was significantly increased. In all cows, the decreased ratio of the VLDL-TG concentration in HB to the non-esterified fatty acids (NEFA) concentration in portal blood (PB) on day 4 appeared to reflect relatively decreased secretion of TG as VLDL by NEFA excessively mobilized to the liver via PB. The markedly increased ratio on day 10 was considered to contribute to the improvement of hepatic lipidosis.

  12. LDL cholesterol goals and cardiovascular risk during statin treatment

    DEFF Research Database (Denmark)

    Olsson, Anders G; Lindahl, Christina; Holme, Ingar

    2011-01-01

    We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how...

  13. Effect of I125 on oxidation behavior of lipoprotein subpopulations

    International Nuclear Information System (INIS)

    Majtenyi, S.

    2002-07-01

    Lipoproteins play a central role in lipid metabolism. They serve as a transport vehicle for cholesterol and triglycerides keeping them in plasma in solution. Lipoproteins are characterized by the content of specific apoproteins and differences in the hydrated density ranges. Moreover, they are distinguished by electrophoretic mobility and other characteristics as high and low-density lipoproteins, respectively lipoprotein (a). More specifically, HDL is classified into HDL 2 and HDL 3 . In atherogenesis, lipoproteins are considered to play a key-role. Oxidatively modified LDL is selectively taken up via scavenger receptors of the macrophage-monocyte system. These cells are transformed into foam cells promoting atherogenesis in vessels in the subendothelial space. Oxidized HDL essentially appears to loose its protective effects on LDL and its beneficial function in reverse cholesterol transport. Thus, it turns proatherogenic. The effects various species of free radicals exert on lipoproteins are the reason for this oxidative modification. Thyroid function also influences lipoproteins in a complex manner. Based on their hydrated density ranges, lipoprotein subpopulations were fractionated and isolated via isopycnic density gradient ultracentrifugation. After investigation of the general oxidation behavior, initiated by addition of CuSO 4 to the isolated samples of HDL 3 , HDL 2 , LDL and Lp(a), the influence of different activities of radioiodine-125 on the kinetics of the formation of conjugated dienes was assessed. This was achieved by coincubation of plasma with I 125 . The spectrophotometrical measurement of the concentration of conjugated dienes in the course of CuSO 4 -induced lipid peroxidation leads to measurable changes in absorption at 234 nm. These changes in absorption over time result in a characteristically shaped curve graphically plotted. The shape of these curves mirrors different indicators of lipid peroxidation. Therefrom lag time, maximal

  14. The dynamin chemical inhibitor dynasore impairs cholesterol trafficking and sterol-sensitive genes transcription in human HeLa cells and macrophages.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Girard

    Full Text Available Intracellular transport of cholesterol contributes to the regulation of cellular cholesterol homeostasis by mechanisms that are yet poorly defined. In this study, we characterized the impact of dynasore, a recently described drug that specifically inhibits the enzymatic activity of dynamin, a GTPase regulating receptor endocytosis and cholesterol trafficking. Dynasore strongly inhibited the uptake of low-density lipoprotein (LDL in HeLa cells, and to a lower extent in human macrophages. In both cell types, dynasore treatment led to the abnormal accumulation of LDL and free cholesterol (FC within the endolysosomal network. The measure of cholesterol esters (CE further showed that the delivery of regulatory cholesterol to the endoplasmic reticulum (ER was deficient. This resulted in the inhibition of the transcriptional control of the three major sterol-sensitive genes, sterol-regulatory element binding protein 2 (SREBP-2, 3-hydroxy-3-methyl-coenzymeA reductase (HMGCoAR, and low-density lipoprotein receptor (LDLR. The sequestration of cholesterol in the endolysosomal compartment impaired both the active and passive cholesterol efflux in HMDM. Our data further illustrate the importance of membrane trafficking in cholesterol homeostasis and validate dynasore as a new pharmacological tool to study the intracellular transport of cholesterol.

  15. Birth Weight, Cord Blood Lipoprotein and Apolipoprotein Levels in Indian Newborns

    Directory of Open Access Journals (Sweden)

    Simmi Kharb

    2010-01-01

    Full Text Available Objectives: Primordial prevention of chronic disease is of clinical andpublic health importance. Considering the fetal onset of atherosclerosis,we aimed to determine the cord blood level of lipoproteins andapolipoproteins as well as their correlation with birth weight and gestationalage.Methods: This cross-sectional study comprised 100 healthy Indiannewborns. Ten ml. of cord blood was collected from placental end ofumbilical vein. Serum was separated by centrifugation and analyzed onthe same day for lipid profile including total cholesterol (TC, triglycerides(TG, high density lipoprotein- cholesterol (HDL-C, very lowdensity lipoprotein-cholesterol (VLDL and low density lipoproteincholesterol(LDL-C, apolipoproteins A-I and B (ApoA-I, ApoB.Atherogenic index (AI was calculated as the ratio of ApoB to ApoA-I.Results: Cord blood of female newborns had higher TC, HDL-C,LDL-C, Apo A-I, Apo B and AI as compared to male newborns,whereas TG and VLDL-C were higher in male than in female newborns.Significant positive correlation was observed between cordblood Apo A-I and HDL-C (r= 0.45, p0.05.Conclusions: These findings are another confirmatory evidence forthe association of prenatal factors with cord blood lipid profile, andcan serve as starting point for studying lipid transport system changesduring early life.

  16. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  17. Decrease in plasma high-density lipoprotein cholesterol levels at puberty in boys with delayed adolescence: correlation with plasma testosterone levels

    International Nuclear Information System (INIS)

    Kirkland, R.T.; Keenan, B.S.; Probstfield, J.L.; Patsch, W.; Lin, T.L.; Clayton, G.W.; Insull, W. Jr.

    1987-01-01

    A three-phase study tested the hypothesis that the decrease in the high-density lipoprotein cholesterol (HDL-C) level observed in boys at puberty is related to an increase in the plasma testosterone concentration. In phase I, 57 boys aged 10 to 17 years were categorized into four pubertal stages based on clinical parameters and plasma testosterone levels. These four groups showed increasing plasma testosterone values and decreasing HDL-C levels. In phase II, 14 boys with delayed adolescence were treated with testosterone enanthate. Plasma testosterone levels during therapy were in the adult male range. Levels of HDL-C decreased by a mean of 7.4 mg/dL (0.20 mmol/L) and 13.7 mg/dL (0.35 mmol/L), respectively, after the first two doses. In phase III, 13 boys with delayed adolescence demonstrated increasing plasma testosterone levels and decreasing HDL-C levels during spontaneous puberty. Levels of HDL-C and apolipoprotein A-1 were correlated during induced and spontaneous puberty. Testosterone should be considered a significant determinant of plasma HDL-C levels during pubertal development

  18. Inclisiran in Patients at High Cardiovascular Risk with Elevated LDL Cholesterol

    NARCIS (Netherlands)

    Ray, Kausik K.; Landmesser, Ulf; Leiter, Lawrence A.; Kallend, David; Dufour, Robert; Karakas, Mahir; Hall, Tim; Troquay, Roland P. T.; Turner, Traci; Visseren, Frank L. J.; Wijngaard, Peter; Wright, R. Scott; Kastelein, John J. P.

    2017-01-01

    BACKGROUND In a previous study, a single injection of inclisiran, a chemically synthesized small interfering RNA designed to target PCSK9 messenger RNA, was found to produce sustained reductions in low-density lipoprotein (LDL) cholesterol levels over the course of 84 days in healthy volunteers.

  19. Scratching the surface: Regulation of cell surface receptors in cholesterol metabolism

    NARCIS (Netherlands)

    Nelson, J.K.

    2016-01-01

    Elevated plasma levels of low density lipoprotein cholesterol (LDL) are an established risk factor for the development of atherosclerosis and cardiovascular diseases. The LDL-Receptor is a key determinant in regulating LDL levels in plasma, and current lipid-lowering strategies aim to increase its

  20. Effects of short-term niacin treatment on plasma lipoprotein concentrations in African green monkeys (Chlorocebus aethiops)

    KAUST Repository

    Chauke, Chesa G.; Arieff, Zainunisha; Kaur, Mandeep; Seier, Jü rgen V.

    2014-01-01

    Niacin is the most effective drug available for raising levels of high-density lipoprotein (HDL) cholesterol. To evaluate its effects on plasma lipid concentrations, the authors administered a low dose of niacin to healthy, adult, female African

  1. Effects of hormones on lipids and lipoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M.

    1991-12-01

    Levels of plasma lipids and lipoproteins are strong predictors for the development of atherosclerotic cardiovascular disease in postmenopausal women. In women, as in men, numerous factors contribute to variations in plasma lipoproteins that may affect cardiovascular disease risk. These include age, dietary components, adiposity, genetic traits, and hormonal changes. Each of these factors may operate to varying degrees in determining changes in plasma lipoprotein profiles accompanying menopause- Cross-sectional and longitudinal studies have suggested increases in levels of cholesterol, low density lipoproteins (LDL) and triglyceride-rich lipoproteins associated with menopause. High density lipoproteins (HDL), which are higher in women than men and are thought to contribute to relative protection of premenopausal women from cardiovascular disease, remain relatively constant in the years following menopause, although small, and perhaps transient reductions in the HDL{sub 2} subfraction have been reported in relation to reduced estradiol level following menopause. Despite these associations, it has been difficult to determine the role of endogenous hormones in influencing the plasma lipoproteins of postmenopausal women. In principle, the effects of hormone replacement should act to reverse any alterations in lipoprotein metabolism that are due to postmenopausal hormone changes. While there may be beneficial effects on lipoproteins, hormone treatment does not restore a premenopausal lipoprotein profile. Furthermore, it is not dear to what extent exogenous hormone-induced lipoprotein changes contribute to the reduced incidence of cardiovascular disease with hormone replacement therapy.

  2. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

    Directory of Open Access Journals (Sweden)

    Savel J

    2012-06-01

    Full Text Available Julia Savel,1,2 Marianne Lafitte,1 Yann Pucheu,1,3 Vincent Pradeau,1 Antoine Tabarin,2,3 Thierry Couffinhal1,3,41Centre d'Exploration, de Prévention et de Traitement de l'Athérosclérose, Hôpital Cardiologique, 2Service d'endocrinologie, CHU Bordeaux, Université Bordeaux Segalen, Bordeaux, France; 3Université de Bordeaux Adaptation cardiovasculaire à l'ischémie, 4INSERM, Adaptation cardiovasculaire à l'ischémie, U1034, Pessac, FranceAbstract: A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.Keywords: atherosclerosis, LCAT function

  3. Lipoprotein glomerulopathy treated with LDL-apheresis (Heparin-induced Extracorporeal Lipoprotein Precipitation system: a case report

    Directory of Open Access Journals (Sweden)

    Rivasi Paolo

    2009-12-01

    , we believe that renal damage expressed by proteinuria correlates to the levels of lipids and, furthermore, the treatment with HELP-apheresis, by lowering low-density lipoprotein cholesterol and triglycerides, may be considered as a therapeutic option in synergy with pharmacological treatment in the treatment of lipoprotein glomerulopathy.

  4. Targeting low-density lipoprotein receptors with protein-only nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Zhikun [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain); Céspedes, María Virtudes [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Unzueta, Ugutz [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain); Álamo, Patricia [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Pesarrodona, Mireia [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain); Mangues, Ramón [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Spain); Vázquez, Esther; Villaverde, Antonio, E-mail: antoni.villaverde@uab.cat; Ferrer-Miralles, Neus, E-mail: neus.ferrer@uab.cat [Universitat Autònoma de Barcelona, Institut de Biotecnologia i de Biomedicina (Spain)

    2015-03-15

    Low-density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood–brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and cost-effective bioproduction, and full biocompatibility. In this study, we have designed and characterized several chimerical proteins containing different LDLR ligands, regarding their ability to bind and internalize target cells and to self-organize as viral mimetic nanoparticles of about 18 nm in diameter. While the self-assembling of LDLR-binding proteins as nanoparticles positively influences cell penetration in vitro, the nanoparticulate architecture might be not favoring BBB crossing in vivo. These findings are discussed in the context of the use of nanostructured materials as vehicles for the systemic treatment of CNS diseases.

  5. Targeting low-density lipoprotein receptors with protein-only nanoparticles

    International Nuclear Information System (INIS)

    Xu, Zhikun; Céspedes, María Virtudes; Unzueta, Ugutz; Álamo, Patricia; Pesarrodona, Mireia; Mangues, Ramón; Vázquez, Esther; Villaverde, Antonio; Ferrer-Miralles, Neus

    2015-01-01

    Low-density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood–brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and cost-effective bioproduction, and full biocompatibility. In this study, we have designed and characterized several chimerical proteins containing different LDLR ligands, regarding their ability to bind and internalize target cells and to self-organize as viral mimetic nanoparticles of about 18 nm in diameter. While the self-assembling of LDLR-binding proteins as nanoparticles positively influences cell penetration in vitro, the nanoparticulate architecture might be not favoring BBB crossing in vivo. These findings are discussed in the context of the use of nanostructured materials as vehicles for the systemic treatment of CNS diseases

  6. Alpha slow-moving high-density-lipoprotein subfraction in serum of a patient with radiation enteritis and peritoneal carcinosis

    International Nuclear Information System (INIS)

    Peynet, J.; Legrand, A.; Messing, B.; Thuillier, F.; Rousselet, F.

    1989-01-01

    An alpha slow-moving high-density-lipoprotein (HDL) subfraction was seen in a patient presenting with radiation enteritis and peritoneal carcinosis, who was given long-term cyclic parenteral nutrition. This subfraction, observed in addition to normal HDL, was precipitated with low-density lipoproteins (LDL) and very-low-density lipoproteins (VLDL) by sodium phosphotungstate-magnesium chloride. The patient's serum lipoproteins were analyzed after fractionation by density gradient ultracentrifugation. The alpha slow-moving HDL floated in the ultracentrifugation subfractions with densities ranging from 1.028 to 1.084 kg/L, and their main apolipoproteins included apolipoprotein E in addition to apolipoprotein A-I. These HDL were larger than HDL2. The pathogenesis of this unusual HDL subfraction is hypothesized

  7. Association between cholesterol plasma levels and craving among heroin users.

    Science.gov (United States)

    Lin, Shih-Hsien; Yang, Yen Kuang; Lee, Sheng-Yu; Hsieh, Pei Chun; Chen, Po See; Lu, Ru-Band; Chen, Kao Chin

    2012-12-01

    Lipids may play some roles in the central nervous system functions that are associated with drug addiction. To date, cholesterol is known to influence relapse of cocaine use. However, the relationship between cholesterol and heroin craving is unclear. This study examined the concurrent association between cholesterol and craving. The serum lipid levels of 70 heroin users who were undergoing or had undergone a methadone maintenance therapy were measured. Their craving and demographic data were assessed. Total cholesterol and low-density lipoprotein cholesterol are negatively associated with craving before (r = -0.33, P cognitive aspect of craving and may be a potential marker to predict risk of drug relapse.

  8. Association Between Lipoprotein(A) and Small Apo(A) Phenotypes and Coronary Heart Disease in Sudanese Diabetic Patients

    International Nuclear Information System (INIS)

    Ahmed, A.M.; Elabid, B.E.H.; Addalla, M.A.

    2013-01-01

    Background:Recent studies indicate an independent association of apolipoprotein(a) small phenotypes with the diabetes and the onset of coronary heart disease.Apolipoprotein(a)small phenotypes when used together with Lipoprotein(a) levels make powerful markers in assessing the actual risk of developing coronary heart disease in diabetic patients. Objectives: Evaluation of clinical and diagnostic significant of Lipoprotein(a) levels and apolipoprotein(a) small phenotypes and its relation to coronary heart disease in Sudanese diabetic patients. Setting and duration of study: Diabetic patients attending hospitals and medical centers from May 2011-December 2012, in Khartoum, Sudan. Patients and Methods: This was a case control, hospital based study done on 138 Sudanese diabetic patients attending hospitals and medical centers in Khartoum. Patients were divided into 2 groups. One group had diabetic cases with coronary heart disease and the other were diabetic patients without coronary heart disease. Controls were age and gender matched. Blood samples were collected from both groups(patients and controls) and were run for apolipoproteins, lipoproteins and apolipoprotein(a) small phenotype,low-density lipoprotein,high-density lipoprotein and trigeminal ganglia. Results: The levels of Lipoprotein(a) of patients were significantly higher than controls (p<0.05). Apolipoprotein(a)small phenotype distribution showed a significant difference when compared between patients of both groups (diabetics with and without coronary heart disease) and controls (p<0.05). Both low-density lipoprotein and high-density lipoprotein cholesterol showed significant difference in both patient groups and controls (p<0.05). Total cholesterol and triglyceride levels showed no significant difference between patients and controls. Apolipoprotein(a) small phenotypes showed significant distribution in diabetic patients when compared with coronary heart disease patients (more than one low molecular weight

  9. Impaired low-density lipoprotein receptor activity in chronic B-lymphocytic leukaemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Juliusson, G.; Vitols, S.

    1988-01-01

    Cellular degradation of /sup 125/I-labelled low-density lipoprotein (LDL) was analysed in freshly isolated blood mononuclear cells from 26 patients with chronic B-lymphocytic leukaemia (CLL) and 8 healthy subjects, and in cells following 1,2 and 3 d of culture in medium containing 10% human lipoprotein-deficient serum (LPDS). Fresh CLL cells had lower LDL degradation rates than mononuclear cells from healthy subjects (p < 0.01). The LDL degradation rates increased during culture (p < 0.001), but to a lesser degree in CLL cells than in normal blood mononuclear cells (p < 0.001). The cellular degradation rate of /sup 125/I-LDL was markedly inhibited by an excess of unlabelled LDL, indicating that most of the /sup 125/I-LDL that was degraded had been internalized following binding to the LPDS-induced LDL degradation of CLL cells and the thymidine uptake in CLL cell cultures with (r = 0.70, p < 0.001) and without (r = 0.59, p < 0.01) the B cell mitogen, Epstein-Barr virus. The results indicate that LDL receptors might be involved in the regulation of CLL cell proliferation.

  10. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo

    International Nuclear Information System (INIS)

    Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; Hoff, Joerg van den

    2004-01-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ( 18 F) by conjugation with N-succinimidyl-4-[ 18 F]fluorobenzoate ([ 18 F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [ 18 F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [ 18 F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo

  11. Fluorine-18 radiolabeling of low-density lipoproteins: a potential approach for characterization and differentiation of metabolism of native and oxidized low-density lipoproteins in vivo.

    Science.gov (United States)

    Pietzsch, Jens; Bergmann, Ralf; Rode, Katrin; Hultsch, Christina; Pawelke, Beate; Wuest, Frank; van den Hoff, Joerg

    2004-11-01

    Oxidative modification of low-density lipoprotein (LDL) is regarded as a crucial event in atherogenesis. Assessing the metabolic fate of oxidized LDL (oxLDL) in vivo with radiotracer techniques is hindered by the lack of suitable sensitive and specific radiolabeling methods. We evaluated an improved methodology based on the radiolabeling of native LDL (nLDL) and oxLDL with the positron emitter fluorine-18 ((18)F) by conjugation with N-succinimidyl-4-[(18)F]fluorobenzoate ([(18)F]SFB). We investigated whether radiolabeling of LDL induces adverse structural modifications. Results suggest that radiolabeling of both nLDL and oxLDL using [(18)F]SFB causes neither additional oxidative structural modifications of LDL lipids and proteins nor alteration of their biological activity and functionality, respectively. Thus, radiolabeling of LDL using [(18)F]SFB could prove to be a promising approach for studying the kinetics of oxLDL in vivo.

  12. Low density lipoprotein labelling characterizes experimentally induced atherosclerotic lesions in rabbits in vivo as to presence of foam cells and endothelial coverage

    International Nuclear Information System (INIS)

    Virgolini, I.; Sinzinger, H.; Angelberger, P.; O'Grady, J.

    1991-01-01

    The entry of autologous iodine 125 low density lipoprotein ( 125 I-LDL) into the aortic wall in rabbits was measured. After abdominal endothelium abrasion with a Fogarthy catheter the animals were fed at 1% cholesterol-supplemented diet for 4 weeks. The animals were killed 1-48 h after administration of 25 μCi 125 I-LDL. Local entry of radiolabelled LDL was estimated and correlated to endothelial surface lining and foam cell content, both controlled morphologically. Endothelialized segments showed the lowest entry of 125 I-LDL, the maximum uptake was reached at around 8 h. In de-endothelialized segments the entry was higher and the peak later (12 h), while in re-endothelialized segments a continuous increase in 125 I-LDL entry up to 48 h was measured. Number and extent of foam cells correlated with the entry of LDL. The data indicate the usefulnes of LDL radiolabelling for qualitative in vivo information on surface lining and foam cell content. (orig.)

  13. Correlation between Cholesterol, Triglycerides, Calculated, and Measured Lipoproteins: Whether Calculated Small Density Lipoprotein Fraction Predicts Cardiovascular Risks

    Directory of Open Access Journals (Sweden)

    Sikandar Hayat Khan

    2017-01-01

    Full Text Available Background. Recent literature in lipidology has identified LDL-fractions to be more atherogenic. In this regard, small density LDL-cholesterol (sdLDLc has been considered to possess more atherogenicity than other LDL-fractions like large buoyant LDL-cholesterol (lbLDLc. Recently, Srisawasdi et al. have developed a method for calculating sdLDLc and lbLDLc based upon a regression equation. Using that in developing world may provide us with a valuable tool for ASCVD risk prediction. Objective. (1 To correlate directly measured and calculated lipid indices with insulin resistance, UACR, glycated hemoglobin, anthropometric indices, and blood pressure. (2 To evaluate these lipid parameters in subjects with or without metabolic syndrome, nephropathy, and hypertension and among various groups based upon glycated hemoglobin results. Design. Cross-sectional study. Place and Duration of Study. From Jan 2016 to 15 April 2017. Subjects and Methods. Finally enrolled subjects (male: 110, female: 122 were evaluated for differences in various lipid parameters, including measured LDL-cholesterol (mLDLc, HDLc and calculated LDL-cholesterol (cLDLc, non-HDLc, sdLDLC, lbLDLC, and their ratio among subjects with or without metabolic syndrome, nephropathy, glycation index, anthropometric indices, and hypertension. Results. Significant but weak correlation was mainly observed between anthropometric indices, insulin resistance, blood pressure, and nephropathy for non-HDLc, sdLDLc, and sdLDLc/lbLDLc. Generally lipid indices were higher among subjects with metabolic syndrome [{sdLDLc: 0.92 + 0.33 versus 0.70 + 0.29 (p 7.0%. Subjects having nephropathy (UACR > 2.4 mg/g had higher concentration of non-HDLc levels in comparison to sdLDLc [{non-HDLc: 3.68 + 0.59 versus 3.36 + 0.43} (p=0.007, {sdLDLc: 0.83 + 0.27 versus 0.75 + 0.35 (p=NS}]. Conclusion. Lipid markers including cLDLc and mLDLc are less associated with traditional ASCVD markers than non-HDLc, sdLDLc, and sd

  14. Accumulation and interaction of hypericin in low-density lipoprotein--a photophysical study.

    Science.gov (United States)

    Mukherjee, Prasun; Adhikary, Ramkrishna; Halder, Mintu; Petrich, Jacob W; Miskovsky, Pavol

    2008-01-01

    The accumulation and interaction of hypericin with the biologically important macromolecule, low-density lipoprotein (LDL), is investigated using various steady-state and time-resolved fluorescence measurements. It is concluded that multiple hypericins can penetrate considerably deeply into the LDL molecule. Up to approximately 20 nonaggregated hypericin molecules can enter LDL; but upon increasing the hypericin concentration, the fluorescence lifetime of hypericin decreases drastically, suggesting most likely the self-quenching of aggregated hypericin. There is also evidence of energy transfer from tryptophans of the constituent protein, apoB-100, to hypericin in LDL. The results demonstrate the ability of LDL to solubilize hypericin (a known photosensitizer) in nonaggregated form, which has implications for the construction of drug delivery systems.

  15. Trans-intestinal cholesterol effl ux is not mediated through high density lipoprotein

    NARCIS (Netherlands)

    Vrins, C.L.; Ottenhoff, R.; Oever, K. van den; Waart, D.R. de; Kruyt, J.K.; Zhao, Y.; Berkel, T.J. van; Havekes, L.M.; Aerts, J.M.; Eck, M. van; Rensen, P.C.; Groen, A.K.

    2012-01-01

    Transintestinal cholesterol efflux (TICE) provides an attractive target to increase body cholesterol excretion. At present, the cholesterol donor responsible for direct delivery of plasma cholesterol to the intestine is unknown. In this study, we investigated the role of HDL in TICE. ATP-binding

  16. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  17. Metabolism of lipoproteins by human fetal hepatocytes

    International Nuclear Information System (INIS)

    Carr, B.R.

    1987-01-01

    The rate of clearance of lipoproteins from plasma appears to play a role in the development of atherogenesis. The liver may account for as much as two thirds of the removal of low-density lipoprotein and one third of the clearance of high-density lipoprotein in certain animal species and humans, mainly by receptor-mediated pathways. The purpose of the present investigation was to determine if human fetal hepatocytes maintained in vitro take up and degrade lipoproteins. We first determined that the maximal binding capacity of iodine 125-iodo-LDL was approximately 300 ng of low-density lipoprotein protein/mg of membrane protein and an apparent dissociation constant of approximately 60 micrograms low-density lipoprotein protein/ml in membranes prepared from human fetal liver. We found that the maximal uptake of [ 125 I]iodo-LDL and [ 125 I]iodo-HDL by fetal hepatocytes occurred after 12 hours of incubation. Low-density lipoprotein uptake preceded the appearance of degradation products by 4 hours, and thereafter the degradation of low-density lipoprotein increased linearly for at least 24 hours. In contrast, high-density lipoprotein was not degraded to any extent by fetal hepatocytes. [ 125 I]Iodo-LDL uptake and degradation were inhibited more than 75% by preincubation with low-density lipoprotein but not significantly by high-density lipoprotein, whereas [ 125 I]iodo-HDL uptake was inhibited 70% by preincubation with high-density lipoprotein but not by low-density lipoprotein. In summary, human fetal hepatocytes take up and degrade low-density lipoprotein by a receptor-mediated process similar to that described for human extrahepatic tissues

  18. The Role of High-Density Lipoproteins in Reducing the Risk of Vascular Diseases, Neurogenerative Disorders, and Cancer

    Directory of Open Access Journals (Sweden)

    Donovan McGrowder

    2011-01-01

    Full Text Available High-density lipoprotein (HDL is one of the major carriers of cholesterol in the blood. It attracts particular attention because, in contrast with other lipoproteins, as many physiological functions of HDL influence the cardiovascular system in favourable ways unless HDL is modified pathologically. The functions of HDL that have recently attracted attention include anti-inflammatory and anti-oxidant activities. High anti-oxidant and anti-inflammatory activities of HDL are associated with protection from cardiovascular disease. Atheroprotective activities, as well as a functional deficiency of HDL, ultimately depend on the protein and lipid composition of HDL. Further, numerous epidemiological studies have shown a protective association between HDL-cholesterol and cognitive impairment. Oxidative stress, including lipid peroxidation, has been shown to be the mediator of the pathologic effects of numerous risk factors of Alzheimer's disease. Lifestyle interventions proven to increase HDL- cholesterol levels including “healthy” diet, regular exercise, weight control, and smoking cessation have also been shown to provide neuro-protective effects. This review will focus on current knowledge of the beneficial effects of HDL-cholesterol as it relates to cardiovascular diseases, breast and lung cancers, non-Hodgkin's lymphoma, as well as its neuroprotective potential in reducing the risk of Alzheimer's disease and dementia.

  19. Radiolabelled lipoproteins and method for making same

    International Nuclear Information System (INIS)

    Lees, R.S.

    1987-01-01

    A method is described for detecting accumulation of low density lipoproteins in an arterial wall, the method comprising the steps of A. preparing a technetium-99m-labelled low density lipoprotein in a solution having a pH between 8 and 9; B. injecting the labelled low density lipoprotein into the vascular system of a patient; C. subsequently viewing the patient's vascular system with extracorporeally-located detecting means capable of detecting the labelled low density lipoprotein; D. determining from the detecting means the locations of the labelled density lipoproteins; and E. quantifying concentrations of the labelled low density lipoproteins at the locations to determine the accumulation of the lipoproteins

  20. Effect of the Composition of Infusion Media on the Blood Lipoprotein Profile in the Treatment of Gestosis

    Directory of Open Access Journals (Sweden)

    L. N. Shcherbakova

    2009-01-01

    Full Text Available Objective: to study whether reamberin and hydroxyethyl starch may be used to correct dyslipoproteinemia in gestosis. Subjects and methods: Twenty-two patients with early postoperative gestosis were examined. Group 1 patients (n=8 received the standard treatment. In addition to the standard treatment, Group 2 patients (n=7 were given 6% hydroxyethyl starch solution infusion at concentrations of 5-6 ml/kg body weight at a rate of 3 ml/ml. Just after hydroxyethyl starch infusion, Group 3 patients (n=7 were additionally injected 1.5% reamberin by the above scheme. The results of examinations were compared with the data obtained on examination of 8 puerperas after pregnancy and normal delivery (Group 4. The plasma concentration of triglycerides, total cholesterol (TC, and the cholesterols of high-density lipoprotein (HDL, low-density lipoprotein (LDL, and very low-density lipoprotein (VLDL were measured. Results and discussion. All the puerperas with gestosis were found to have hypertriglyceridemia and elevated levels of VLDL cholesterol with decreased concentrations of HDL cholesterol. The moderately higher levels of triglycerides and TC were also observed in patients without gestosis. Hydroxyethyl starch lowered the concentration of triglycerides by postpartum days 3—4. When hydroxyethyl starch was used in combination with reamberin, there was a significant reduction in the concentrations of triglycerides and VLDL and LDL cholesterols and a substantial rise in the level of HDL cholesterol. By postpartum days 3 and 4, Group 1 showed a considerable increase in the atherogenicity coefficient, which was significant as compared with the baseline level. Hydroxyethyl starch alone prevented an increase in the atherogenici-ty coefficient while its use in combination with reamberin significantly lowered this index and normalized it by postpartum days 3—4. Conclusion. Hydroxyethyl starch alone and in combination with reamberin shows an antiatherogenic