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Sample records for high-density lipoprotein cholesterol

  1. High-density lipoprotein cholesterol: How High

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

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    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.

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

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

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    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.

  5. 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

  6. Polygenic determinants in extremes of high-density lipoprotein cholesterol.

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    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; Hegele, Robert A

    2017-11-01

    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. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  7. 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...

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

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    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.

  9. 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

  10. 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

  11. 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

  12. 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)....

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

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    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.

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

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    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.

  15. 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.

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

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    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.

  17. 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.

  18. 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

  19. 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

  20. 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...

  1. 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.

  2. 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

  3. 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

  4. 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...

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  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. 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...

  15. Interaction between TCF7L2 polymorphism and dietary fat intake on high density lipoprotein cholesterol.

    Directory of Open Access Journals (Sweden)

    Dhanasekaran Bodhini

    Full Text Available Recent evidence suggests that lifestyle factors influence the association between the Melanocortin 4 receptor (MC4R and Transcription Factor 7-Like 2 (TCF7L2 gene variants and cardio-metabolic traits in several populations; however, the available research is limited among the Asian Indian population. Hence, the present study examined whether the association between the MC4R single nucleotide polymorphism (SNP (rs17782313 and two SNPs of the TCF7L2 gene (rs12255372 and rs7903146 and cardio-metabolic traits is modified by dietary factors and physical activity. This cross sectional study included a random sample of normal glucose tolerant (NGT (n = 821 and participants with type 2 diabetes (T2D (n = 861 recruited from the urban part of the Chennai Urban Rural Epidemiology Study (CURES. A validated food frequency questionnaire (FFQ was used for dietary assessment and self-reported physical activity measures were collected. The threshold for significance was set at P = 0.00023 based on Bonferroni correction for multiple testing [(0.05/210 (3 SNPs x 14 outcomes x 5 lifestyle factors]. After Bonferroni correction, there was a significant interaction between the TCF7L2 rs12255372 SNP and fat intake (g/day (Pinteraction = 0.0001 on high-density lipoprotein cholesterol (HDL-C, where the 'T' allele carriers in the lowest tertile of total fat intake had higher HDL-C (P = 0.008 and those in the highest tertile (P = 0.017 had lower HDL-C compared to the GG homozygotes. In a secondary analysis of SNPs with the subtypes of fat, there was also a significant interaction between the SNP rs12255372 and polyunsaturated fatty acids (PUFA, g/day (Pinteraction<0.0001 on HDL-C, where the minor allele carriers had higher HDL-C in the lowest PUFA tertile (P = 0.024 and those in the highest PUFA tertile had lower HDL-C (P = 0.028 than GG homozygotes. In addition, a significant interaction was also seen between TCF7L2 SNP rs12255372 and fibre intake (g/day on HDL

  16. 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.

  17. [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.

  18. 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.

  19. 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

    • 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...

  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. 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

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  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. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Oxidation of Cholesterol Does Not Alter Significantly Its Uptake into High-Density Lipoprotein Particles

    Czech Academy of Sciences Publication Activity Database

    Karilainen, T.; Timr, Štěpán; Vattulainen, I.; Jungwirth, Pavel

    2015-01-01

    Roč. 119, č. 13 (2015), s. 4594-4600 ISSN 1520-6106 R&D Projects: GA ČR GBP208/12/G016 Institutional support: RVO:61388963 Keywords : molecular dynamics * free energy profiles * cholesterol Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 3.187, year: 2015

  16. Hip circumference is associated with high density lipoprotein cholesterol response following statin therapy in hypertensive subjects.

    Science.gov (United States)

    Pio-Magalhães, J A; Ferreira-Sae, M C; Souza, F A; Grespan-Magossi, A M; Schreiber, R; Velloso, L A; Geloneze, B; Franchini, K G; Nadruz, W

    2011-10-01

    This report investigated the relationship between anthropometric measurements of body fat distribution and lipid response to statins in hypercholesterolemic hypertensive patients. We prospectively examined 129 subjects who used either simvastatin 20 mg/day (no.=83) or atorvastatin 10 mg/day (no.=46) for 3 months. Anthropometry included evaluation of body mass index, waist and hip circumferences, and waist-to-hip-ratio. Significant decreases in LDL (pcorrelation between waist circumference and HDLcholesterol levels was detected (r=-0.18; p=0.04). Conversely, a direct relationship between hip circumference and HDLcholesterol response to statins was found in the whole sample (r=0.24; p=0.006), while no other anthropometric measurement displayed significant correlation with lipid changes. The association between HDL-cholesterol response and hip circumference was further confirmed by stepwise regression analysis adjusted for baseline HDL-cholesterol levels, metabolic syndrome, body mass index, and waist circumference. Hip circumference, a surrogate marker of peripheral adiposity, is associated with HDL-cholesterol changes following statin therapy in hypertensive patients.

  17. 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

  18. 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.

  19. Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes.

    Science.gov (United States)

    Link, Jenny C; Chen, Xuqi; Prien, Christopher; Borja, Mark S; Hammerson, Bradley; Oda, Michael N; Arnold, Arthur P; Reue, Karen

    2015-08-01

    The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male-female gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed that the male-female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. © 2015 American Heart Association, Inc.

  20. 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.

  1. 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

  2. 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.

  3. Pathways-driven sparse regression identifies pathways and genes associated with high-density lipoprotein cholesterol in two Asian cohorts.

    Directory of Open Access Journals (Sweden)

    Matt Silver

    2013-11-01

    Full Text Available Standard approaches to data analysis in genome-wide association studies (GWAS ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK

  4. 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

  5. Conflicting interactions of apolipoprotein A and high density lipoprotein cholesterol with microvascular complications of type 2 diabetes.

    Science.gov (United States)

    Aryan, Zahra; Afarideh, Mohsen; Ghajar, Alireza; Esteghamati, Sadaf; Esteghamati, Alireza; Nakhjavani, Manouchehr

    2017-11-01

    This study is amid at investigating the associations, and interactions of serum lipid biomarkers with microvascular complications of type 2 diabetes (T2D). A nested case-control study was conducted within an ongoing prospective study on patients with T2D. Microvascular complications of T2D including diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were investigated. A total of 444 cases with at least one of the microvascular complications of T2D and 439 age- and gender-matched controls free of any of the chronic microvascular complications of T2D were included. The associations and interactions of a panel of serum lipid biomarkers with the microvascular complications of T2D were investigated. Serum triglyceride had the strongest association with microvascular complications of T2D (crude model: β=0.632, P value=0.045). Each standard deviation increment in serum TG was associated with 3.7 times increased frequency of microvascular complications. Despite high density lipoprotein cholesterol (HDL-C), serum apolipoprotein A1 (Apo A1) was positively associated with the presence of diabetic neuropathy. Each standard deviation increment in serum ApoA1 was associated with increased frequency of diabetic neuropathy (OR, 1.2, 95% CI, (1.1-1.3), P value=0.006). The frequency of diabetic neuropathy was higher in 2nd and 3rd quartiles of serum Lp(a) compared to diabetic patients in the first quartile (OR, 5.52, 95% (1.17-25.8), P value=0.047). ApoA1 but not HDL-C is straightly associated with diabetic neuropathy. Even Slight rise in serum Lp(a) is associated with increased frequency of diabetic retinopathLipid variables could serve as specific predictors of vascular complications in diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Pathways-Driven Sparse Regression Identifies Pathways and Genes Associated with High-Density Lipoprotein Cholesterol in Two Asian Cohorts

    Science.gov (United States)

    Silver, Matt; Chen, Peng; Li, Ruoying; Cheng, Ching-Yu; Wong, Tien-Yin; Tai, E-Shyong; Teo, Yik-Ying; Montana, Giovanni

    2013-01-01

    Standard approaches to data analysis in genome-wide association studies (GWAS) ignore any potential functional relationships between gene variants. In contrast gene pathways analysis uses prior information on functional structure within the genome to identify pathways associated with a trait of interest. In a second step, important single nucleotide polymorphisms (SNPs) or genes may be identified within associated pathways. The pathways approach is motivated by the fact that genes do not act alone, but instead have effects that are likely to be mediated through their interaction in gene pathways. Where this is the case, pathways approaches may reveal aspects of a trait's genetic architecture that would otherwise be missed when considering SNPs in isolation. Most pathways methods begin by testing SNPs one at a time, and so fail to capitalise on the potential advantages inherent in a multi-SNP, joint modelling approach. Here, we describe a dual-level, sparse regression model for the simultaneous identification of pathways and genes associated with a quantitative trait. Our method takes account of various factors specific to the joint modelling of pathways with genome-wide data, including widespread correlation between genetic predictors, and the fact that variants may overlap multiple pathways. We use a resampling strategy that exploits finite sample variability to provide robust rankings for pathways and genes. We test our method through simulation, and use it to perform pathways-driven gene selection in a search for pathways and genes associated with variation in serum high-density lipoprotein cholesterol levels in two separate GWAS cohorts of Asian adults. By comparing results from both cohorts we identify a number of candidate pathways including those associated with cardiomyopathy, and T cell receptor and PPAR signalling. Highlighted genes include those associated with the L-type calcium channel, adenylate cyclase, integrin, laminin, MAPK signalling and immune

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol

  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. 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.

  16. 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

  17. 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 ...

  18. 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.

  19. 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.

  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. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. [Relationship between the triglyceride/high-density lipoprotein-cholesterol ratio, insulin resistance index and cardiometabolic risk factors in women with polycystic ovary syndrome].

    Science.gov (United States)

    Roa Barrios, Marlene; Arata-Bellabarba, Gabriela; Valeri, Lenin; Velázquez-Maldonado, Elsy

    2009-02-01

    To evaluate the relationship between the triglyceride/high density lipoprotein cholesterol (TG/HDL-c) ratio, insulin resistance index and cardiometabolic risk factors in women with polycystic ovary syndrome (PCOS). The present crosssectional study analyzed 62 women with PCOS and 48 healthy women (control group) aged 17- 35 years old. Body mass index (BMI), waist circumference (WC) and blood pressure were registered. Plasma concentrations of glucose, insulin, triglycerides, total cholesterol and HDL-c were measured. TheTG/HDL-c ratio, homeostasis model assessment for insulin resistance (HOMA(IR)) and quantitative insulin sensitivity check index (QUICKI) were calculated. Women with PCOS showed significantly higher values of the TG/HDL-c ratio and HOMA(IR), and a significantly lower QUICKI value. These differences were related to BMI and WC, with the highest values being observed in obese patients. The 50th percentile for the TG/HDL-c ratio was 3.64; the TG/cHDL ratio was positively correlated with BMI, WC and HOMA(IR) (r=0.48, pglucose > 100 mg/dl (10% vs 3%; ptriglycerides>150 mg/dl (55% vs 20%; p80 cm (82.3% vs 43.8%; pindexes (HOMA(IR), QUICKI). The TG/HDL-c ratio could be considered as a useful and practical method to identify an increased risk of cardiovascular disease in patients with PCOS.

  7. Physical activity, high density lipoprotein cholesterol and other lipids levels, in men and women from the ATTICA study

    Directory of Open Access Journals (Sweden)

    Papaioannou Ioanna

    2003-06-01

    Full Text Available Abstract Background Physical activity has long been associated with reduced risk of coronary heart disease (CHD. In this work we evaluated the effect of physical activity on lipid levels, in a sample of cardiovascular disease free people. Methods The ATTICA study is a population – based cohort that has randomly enrolled 2772 individuals, stratified by age – gender (according to the census 2001, from the greater area of Athens, during 2001–2002. Of them, 1376 were men (45 ± 12 years old, range: 18 – 86 and 1396 women (45 ± 13 years old, range: 18 – 88. We assessed the relationship between physical activity status (measured in kcal/min expended per day and several lipids, after taking into account the effect of several characteristics of the participants. Results 578 (42% men and 584 (40% women were classified as physically active. Compared to sedentary physically active women had significantly lower levels of total serum cholesterol (p Conclusions Substantial independent increases in HDL-cholesterol and apolipoprotein A1 concentrations were observed in women, but not in men, in a Mediterranean cohort.

  8. Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans.

    Science.gov (United States)

    Choi, Hyung Jin; Cho, Young Min; Moon, Min Kyong; Choi, Hye Hun; Shin, Hyoung Doo; Jang, Hak Chul; Kim, Seong Yeon; Lee, Hong Kyu; Park, Kyong Soo

    2006-11-01

    Ghrelin is known to play a role in glucose metabolism and in beta-cell function. There are controversies regarding the role of ghrelin polymorphisms in diabetes and diabetes-related phenotypes. The objective of this study was to examine polymorphisms of the ghrelin gene in a Korean cohort and investigate associations between them and susceptibility to type 2 diabetes and its related phenotypes. The ghrelin gene was sequenced to identify polymorphisms in 24 DNA samples. Common variants were then genotyped in 760 type 2 diabetic patients and 641 nondiabetic subjects. Genetic associations with diabetes-related phenotypes were also analyzed. Nine polymorphisms were identified, and four common polymorphisms [g.-1500C>G, g.-1062G > C, g.-994C > T, g.+408C > A (Leu72Met)] were genotyped in a larger study. The genotype distributions of these four common polymorphisms in type 2 diabetes patients were similar to those of normal nondiabetic controls. However, these four common polymorphisms were variably associated with several diabetes-related phenotypes, such as high-density lipoprotein (HDL) cholesterol, fasting plasma glucose, and homeostasis model assessment of insulin resistance. In particular, subjects harboring g.-1062C were associated with a lower serum HDL cholesterol level after adjusting for other variables (P = 0.0004 or 0.01 after Bonferroni correction for 24 tests). The aforementioned four common polymorphisms in the ghrelin gene were not found to be significantly associated with susceptibility to type 2 diabetes mellitus in the Korean population. However, the common polymorphism g.-1062G > C in the promoter region of the ghrelin gene was found to be significantly associated with serum HDL cholesterol levels.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. Association between serum triglyceride to high-density lipoprotein cholesterol ratio and sarcopenia in elderly Korean males: The Korean National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Chung, Tae-Ha; Kwon, Yu-Jin; Shim, Jae-Yong; Lee, Yong-Jae

    2016-12-01

    We investigated the association between the triglycerides to high-density lipoprotein cholesterol (TG/HDL) ratio and sarcopenia in elderly Korean males. We examined the relationship between the TG/HDL ratio and sarcopenia in 879 elderly males ≥60years who participated in the 2010-2011 KNHANES. Sarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by the weight (%), which is >1 SD below the mean for young adults. The odds ratios (ORs) for sarcopenia were calculated using multiple logistic regression across the TG/HDL ratio quartiles (Q1: ≤1.4, Q2: 1.5-2.4, Q3: 2.5-3.8 and Q4: ≥3.9) after adjusting for confounding variables. The prevalence of sarcopenia significantly increased in accordance with TG/HDL ratio quartiles. Compared with the lowest quartile of the TG/HDL ratio, the corresponding OR (95% CI) of the highest quartile of the TG/HDL ratio for sarcopenia was 2.10 (1.12-3.91) after adjusting for age, body mass index (BMI), cigarette smoking, alcohol intake and physical activity. TG/HDL ratio was positively related with a higher risk of sarcopenia in elderly Korean males. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Effects of red grape juice consumption on high density lipoprotein-cholesterol, apolipoprotein AI, apolipoprotein B and homocysteine in healthy human volunteers.

    Science.gov (United States)

    Khadem-Ansari, Mohammad H; Rasmi, Yousef; Ramezani, Fatemeh

    2010-01-01

    It has suggested that grape juice consumption has lipid- lowering effect and it is associated with a decreased risk of heart disease. We aimed to evaluate the effects of red grape juice (RGj) consumption on high density lipoprotein-cholesterol (HDL-C), apolipoprotein AI (apoAI), apolipoprotein B (apoB) and homocysteine (Hcy) levels in healthy human volunteers. Twenty six healthy and nonsmoking males, aged between 25-60 years, who were under no medication asked to consume 150 ml of RGj twice per day for one month. Serum HDL-C, apoAI, apoB and plasma Hcy levels were measured before and after one month RGj consumption. HDL-C levels after RGj consumption were significantly higher than the corresponding levels before the RGj consumption (41.44 ± 4.50 and 44.37 ± 4.30 mg/dl; P0.05). Hcy levels were decreased after RGj consumption (7.70 ± 2.80 and 6.20 ± 2.30 µmol/l; P<0.001). The present study demonstrates that RGj consumption can significantly increase serum HDL-C levels and decrease Hcy levels. These findings may have important implications for the prevention of atherosclerosis in healthy individuals.

  15. 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

  16. Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol.

    Science.gov (United States)

    Abbasi, Fahim; Reaven, Gerald M

    2011-12-01

    The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with SSPG (r ∼ 0.75, P index, homeostasis model assessment of insulin resistance, and fasting TG and insulin (r ∼ 0.60, P index correlated with SSPG concentration to a similar degree, and the relationships were comparable to estimates using fasting insulin. The strongest relationship was between SSPG and insulin-AUC. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 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...

  18. 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.

  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. 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

  2. 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

  3. Triglyceride-to-high-density-lipoprotein-cholesterol ratio is an index of heart disease mortality and of incidence of type 2 diabetes mellitus in men.

    Science.gov (United States)

    Vega, Gloria Lena; Barlow, Carolyn E; Grundy, Scott M; Leonard, David; DeFina, Laura F

    2014-02-01

    High triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) impart risk for heart disease. This study examines the relationships of TG/HDL-C ratio to mortality from all causes, coronary heart disease (CHD), or cardiovascular disease (CVD). Survival analysis was done in 39,447 men grouped by TG/HDL-C ratio cut point of 3.5 and for metabolic syndrome. National Death Index International Classification of Diseases (ICD-9 and ICD-10) codes were used for CVD and CHD deaths occurring from 1970 to 2008. Incidence of type 2 diabetes mellitus (DM) according to ratio was estimated in 22,215 men. Triglyceride/HDL-C ratio and cross-product of TG and fasting blood glucose (TyG index) were used in analysis. Men were followed up for 581,194 person-years. Triglyceride/HDL-C ratio predicted CHD, CVD, and all-cause mortality after adjustment for established risk factors and non-HDL-C. Mortality rates were higher in individuals with a high ratio than in those with a low ratio. Fifty-five percent of men had metabolic syndrome that was also predictive of CHD, CVD, and all-cause mortality. Annual incidence of DM was 2 times higher in men with high TG/HDL-C ratio than in those with a low ratio. Individuals with high TG/HDL-C ratio had a higher incidence of DM than those with a low ratio. The TyG index was not equally predictive of causes of mortality to TG/HDL-C, but both were equally predictive of diabetes incidence. Triglyceride/HDL-C ratio predicts CHD and CVD mortality as well as or better than do metabolic syndrome in men. Also, a high ratio predisposes to DM. The TyG index does not predict CHD, CVD, or all-cause mortality equally well, but like TG/HDL-C ratio, it predicts DM incidence.

  4. The triglyceride/high-density lipoprotein cholesterol ratio fails to predict insulin resistance in African-American women: an analysis of Jackson Heart Study.

    Science.gov (United States)

    Sumner, Anne E; Harman, Jane L; Buxbaum, Sarah G; Miller, Bernard V; Tambay, Anita V; Wyatt, Sharon B; Taylor, Herman A; Rotimi, Charles N; Sarpong, Daniel F

    2010-12-01

    Compared to whites, insulin-resistant African Americans have worse outcomes. Screening programs that could identify insulin resistance early enough for intervention to affect outcome often rely on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels. Racial differences in TG and HDL-C may compromise the efficacy of these programs in African Americans. A recommendation currently exists to use the TG/HDL-C ratio ≥2.0 to predict insulin resistance in African Americans. The validity of this recommendation needs examination. Therefore, our aim was to determine the ability of TG/HDL-C ratio to predict insulin resistance in African Americans. In 1,903 African Americans [895 men, 1,008 women, age 55 ± 12 years, mean ± standard deviation (SD), range 35-80 years, body mass index (BMI) 31.0 ± 6.4 kg/m(2), range 18.5-55 kg/m(2)] participating in the Jackson Heart Study, a population-based study of African Americans, Jackson, Mississippi tricounty region, insulin resistance was defined by the upper quartile (≥4.43) of homeostasis model assessment of insulin resistance (HOMA-IR). An area under the receiver operating characteristic curve (AUC-ROC) of >0.70 was required for prediction of insulin resistance by TG/HDL-C. The optimal test cutoff was determined by the Youden index. HOMA-IR was similar in men and women (3.40 ± 2.03 vs. 3.80 ± 2.46, P = 0.60). Women had lower TG (94 ± 49 vs. 109 ± 65 mg/dL P Heart Study can help determine the efficacy of screening programs in African-Americans.

  5. [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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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.

  12. 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

  13. Biomimetic High-Density Lipoproteins from a Gold Nanoparticle Template

    Science.gov (United States)

    Luthi, Andrea Jane

    For hundreds of years the field of chemistry has looked to nature for inspiration and insight to develop novel solutions for the treatment of human diseases. The ability of chemists to identify, mimic, and modifiy small molecules found in nature has led to the discovery and development of many important therapeutics. Chemistry on the nanoscale has made it possible to mimic natural, macromolecular structures that may also be useful for understanding and treating diseases. One example of such a structure is high-density lipoprotein (HDL). The goal of this work is to use a gold nanoparticle (Au NP) as a template to synthesize functional mimics of HDL and characterize their structure and function. Chapter 1 details the structure and function of natural HDL and how chemistry on the nanoscale provides new strategies for mimicking HDL. This Chapter also describes the first examples of using nanoparticles to mimic HDL. Chapter 2 reports the synthesis and characterization of biomimetic HDL using different sizes of Au NPs and different surface chemistries and how these variables can be used to tailor the properties of biomimetic HDL. From these studies the optimal strategy for synthesizing biomimetic HDL was determined. In Chapter 3, the optimization of the synthesis of biomimetic HDL is discussed as well as a full characterization of its structure. In addition, the work in this chapter shows that biomimetic HDL can be synthesized on a large scale without alterations to its structure or function. Chapter 4 focuses on understanding the pathways by which biomimetic HDL accepts cholesterol from macrophage cells. The results of these studies demonstrate that biomimetic HDL is able to accept cholesterol by both active and passive pathways of cholesterol efflux. In Chapter 5 the preliminary results of in vivo studies to characterize the pharmacokinetics and pharmacodynamics of biomimetic HDL are presented. These studies suggest that biomimetic HDL traffics through tissues prone to

  14. Gene-gene combination effect and interactions among ABCA1, APOA1, SR-B1, and CETP polymorphisms for serum high-density lipoprotein-cholesterol in the Japanese population.

    Directory of Open Access Journals (Sweden)

    Akihiko Nakamura

    Full Text Available BACKGROUND/OBJECTIVE: Gene-gene interactions in the reverse cholesterol transport system for high-density lipoprotein-cholesterol (HDL-C are poorly understood. The present study observed gene-gene combination effect and interactions between single nucleotide polymorphisms (SNPs in ABCA1, APOA1, SR-B1, and CETP in serum HDL-C from a cross-sectional study in the Japanese population. METHODS: The study population comprised 1,535 men and 1,515 women aged 35-69 years who were enrolled in the Japan Multi-Institutional Collaborative Cohort (J-MICC Study. We selected 13 SNPs in the ABCA1, APOA1, CETP, and SR-B1 genes in the reverse cholesterol transport system. The effects of genetic and environmental factors were assessed using general linear and logistic regression models after adjusting for age, sex, and region. PRINCIPAL FINDINGS: Alcohol consumption and daily activity were positively associated with HDL-C levels, whereas smoking had a negative relationship. The T allele of CETP, rs3764261, was correlated with higher HDL-C levels and had the highest coefficient (2.93 mg/dL/allele among the 13 SNPs, which was statistically significant after applying the Bonferroni correction (p<0.001. Gene-gene combination analysis revealed that CETP rs3764261 was associated with high HDL-C levels with any combination of SNPs from ABCA1, APOA1, and SR-B1, although no gene-gene interaction was apparent. An increasing trend for serum HDL-C was also observed with an increasing number of alleles (p<0.001. CONCLUSIONS: The present study identified a multiplier effect from a polymorphism in CETP with ABCA1, APOA1, and SR-B1, as well as a dose-dependence according to the number of alleles present.

  15. 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

  16. Consistency of genetic inheritance mode and heritability patterns of triglyceride vs. high density lipoprotein cholesterol ratio in two Taiwanese family samples

    Directory of Open Access Journals (Sweden)

    Yang Chi-Yu

    2003-04-01

    Full Text Available Abstract Background Triglyceride/HDL cholesterol ratio (TG/HDL-C is considered as a risk factor for cardiovascular events. Genetic components were important in controlling the variation in western countries. But the mode of inheritance and family aggregation patterns were still unknown among Asian-Pacific countries. This study, based on families recruited from community and hospital, is aimed to investigate the mode of inheritance, heritability and shared environmental factors in controlling TG/HDL-C. Results Two populations, one from community-based families (n = 988, 894 parent-offspring and 453 sibling pairs and the other from hospital-based families (n = 1313, 76 parent-offspring and 52 sibling pairs were sampled. The population in hospital-based families had higher mean age values than community-based families (54.7 vs. 34.0. Logarithmic transformed TG/ HDL-C values, after adjusted by age, gender and body mass index, were for genetic analyses. Significant parent-offspring and sibling correlations were also found in both samples. The parent-offspring correlation coefficient was higher in the hospital-based families than in the community-based families. Genetic heritability was higher in community-based families (0.338 ± 0.114, p = 0.002, but the common shared environmental factor was higher in hospital-based families (0.203 ± 0.042, p Conclusion Variations of TG/HDL-C in the normal ranges were likely to be influenced by multiple factors, including environmental and genetic components. Higher genetic factors were proved in younger community-based families than in older hospital-based families.

  17. Triglycerides/High density lipoprotein cholesterol ratio as a cardiometabolic risk marker in children and adolescents from Mérida city, Venezuela.

    Science.gov (United States)

    Aguirre, Miguel; Briceño, Yajaira; Gómez-Pérez, Roald; Zerpa, Yajaira; Camacho, Nolis; Paoli, Mariela

    2018-02-01

    To determine the behavior of the triglycerides/HDL-cholesterol ratio (TG/HDL) as a cardiometabolic risk marker in children and adolescents from Mérida, Venezuela. A total of 1292 children and adolescents aged 7-18 years who attended educational institutions in the Libertador Municipality were enrolled into this study. Anthropometric measurements and blood pressure values were recorded. Fasting blood glucose, insulin and lipid levels were measured. The TG/HDL ratio, HOMA-IR, and QUICKI indexes were calculated. Subjects were categorized as with and without cardiometabolic risk based on the presence or absence of 2or more risk factors. Cut-off points for the TG/HDL ratio were determined by constructing ROC curves. Significantly higher mean TG/HDL ratios were found in pubertal (2.2 ± 1.7) as compared to prepubertal subjects (1.8 ± 1.5; P=.001), with no sex differences. Two or more risk factors were found in 14.7% (n=192) of the participants, in whom TG/HDL ratios were significantly higher as compared to those with no risk (3.5±2.9 versus 1.6±0.8 in prepubertal and 4.1 ± 3.5 versus 1.8 ± 0.9 in pubertal subjects; P=.0001). According to cardiometabolic risk, cut-off points for the TG/HDL ratio of 1.8 and 2.5 were found for prepubertal and pubertal children respectively. These cut-off points showed risks (odds ratio) higher than 2.5 for conditions such as metabolic syndrome, elevated non-HDL-C, abdominal obesity, and elevated HOMA-IR. In this sample of children and adolescents, an elevated TG/HDLc ratio was found to be a good marker for predicting cardiometabolic risk. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Human endothelial progenitor cells internalize high-density lipoprotein.

    Directory of Open Access Journals (Sweden)

    Kaemisa Srisen

    Full Text Available Endothelial progenitor cells (EPCs originate either directly from hematopoietic stem cells or from a subpopulation of monocytes. Controversial views about intracellular lipid traffic prompted us to analyze the uptake of human high density lipoprotein (HDL, and HDL-cholesterol in human monocytic EPCs. Fluorescence and electron microscopy were used to investigate distribution and intracellular trafficking of HDL and its associated cholesterol using fluorescent surrogates (bodipy-cholesterol and bodipy-cholesteryl oleate, cytochemical labels and fluorochromes including horseradish peroxidase and Alexa Fluor® 568. Uptake and intracellular transport of HDL were demonstrated after internalization periods from 0.5 to 4 hours. In case of HDL-Alexa Fluor® 568, bodipy-cholesterol and bodipy-cholesteryl oleate, a photooxidation method was carried out. HDL-specific reaction products were present in invaginations of the plasma membrane at each time of treatment within endocytic vesicles, in multivesicular bodies and at longer periods of uptake, also in lysosomes. Some HDL-positive endosomes were arranged in form of "strings of pearl"- like structures. HDL-positive multivesicular bodies exhibited intensive staining of limiting and vesicular membranes. Multivesicular bodies of HDL-Alexa Fluor® 568-treated EPCs showed multilamellar intra-vacuolar membranes. At all periods of treatment, labeled endocytic vesicles and organelles were apparent close to the cell surface and in perinuclear areas around the Golgi apparatus. No HDL-related particles could be demonstrated close to its cisterns. Electron tomographic reconstructions showed an accumulation of HDL-containing endosomes close to the trans-Golgi-network. HDL-derived bodipy-cholesterol was localized in endosomal vesicles, multivesicular bodies, lysosomes and in many of the stacked Golgi cisternae and the trans-Golgi-network Internalized HDL-derived bodipy-cholesteryl oleate was channeled into the lysosomal

  19. 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

  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. Role of Lipids in Spheroidal High Density Lipoproteins

    NARCIS (Netherlands)

    Vuorela, Timo; Catte, Andrea; Niemela, Perttu S.; Hall, Anette; Hyvonen, Marja T.; Marrink, Siewert-Jan; Karttunen, Mikko; Vattulainen, Ilpo

    2010-01-01

    We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules

  2. Role of lipids in spheroidal high density lipoproteins

    NARCIS (Netherlands)

    Vuorela, T.A.; Catte, A.; Niemelä, P.S.; Hall, A.; Hyvönen, M.T.; Marrink, S.J.; Karttunen, M.E.J.; Vattulainen, I.

    2010-01-01

    We study the structure and dynamics of spherical high density lipoprotein (HDL) particles through coarse-grained multi-microsecond molecular dynamics simulations. We simulate both a lipid droplet without the apolipoprotein A-I (apoA-I) and the full HDL particle including two apoA-I molecules

  3. Triglyceride to high density lipoprotein cholesterol ratio and its association with periodontal disease in Korean adults: findings based on the 2012-2014 Korean national health and nutrition examination survey.

    Science.gov (United States)

    Kwon, Yu-Jin; Park, Jeong-Won; Lim, Hyoung-Ji; Lee, Yong-Jae; Lee, Hye-Sun; Shim, Jae-Yong

    2018-01-01

    The aim of this study is to evaluate whether the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with periodontal disease in Korean adults. This cross-sectional study included 12,249 individuals (4,941 men and 7,308 women) who took part in the 2012-2014 Korean National Health and Nutrition Examination Survey. We categorized the TG/HDL-C ratio into three groups. Periodontal disease was defined as a community pocket index score ≥3 with at least one affected site. Multiple logistic analyses were used to analyze the association between TG/HDL-C ratio and periodontal disease. In the study population, prevalence of periodontal disease was 31.6% in men and 21% in women. Compared to the lowest tertile group, OR (95% CI) of the highest tertile group for periodontal disease was 1.474 (1.220-1.780) in men and 1.259 (1.041-1.522) in women after adjusting for age, waist circumference, systolic blood pressure, fasting glucose, current smoking, alcohol drinking, physical activity, household income, oral health behavior, and use of anti-dyslipidemia medication. Our study suggests that the TG/HDL-C ratio is associated with periodontal disease in Korean adults. TG/HDL-C ratio is a simple and useful marker to reflect insulin resistance. And periodontal disease is also known to be related with insulin resistance. This study indicates that TG/HDL-C ratio was associated with periodontal disease in Korean adults.

  4. 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...

  5. 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

  6. Atorvastatin affects low density lipoprotein and non-high density lipoprotein cholesterol relations with apolipoprotein B in type 2 diabetes mellitus : modification by triglycerides and cholesteryl ester transfer protein

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; Zwang, Louwerens; Huisman, Menno V.; Banga, Jan Dirk; Sluiter, Wim. J.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    Objectives: Non-HDL-cholesterol (non-HDL-C) and apolipoprotein (apo) B are proposed as treatment targets. The extent to which statin therapy affects relationships of LDL-C and non-HDL-C with apoB was examined in type 2 diabetes. Methods: Analyses were performed in 217 hypertriglyceridaemic type 2

  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. A high-density lipoprotein-mediated drug delivery system.

    Science.gov (United States)

    Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

    2016-11-15

    High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. 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

  10. 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)....

  11. 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.

  12. Biomimetic High Density Lipoprotein Nanoparticles For Nucleic Acid Delivery

    Science.gov (United States)

    McMahon, Kaylin M.; Mutharasan, R. Kannan; Tripathy, Sushant; Veliceasa, Dorina; Bobeica, Mariana; Shumaker, Dale K.; Luthi, Andrea J.; Helfand, Brian T.; Ardehali, Hossein; Mirkin, Chad A.; Volpert, Olga; Thaxton, C. Shad

    2014-01-01

    We report a gold nanoparticle-templated high density lipoprotein (HDL AuNP) platform for gene therapy which combines lipid-based nucleic acid transfection strategies with HDL biomimicry. For proof-of-concept, HDL AuNPs are shown to adsorb antisense cholesterylated DNA. The conjugates are internalized by human cells, can be tracked within cells using transmission electron microscopy (TEM), and regulate target gene expression. Overall, the ability to directly image the AuNP core within cells, the chemical tailorability of the HDL AuNP platform, and the potential for cell-specific targeting afforded by HDL biomimicry make this platform appealing for nucleic acid delivery. PMID:21319839

  13. Differential impact of serum glucose, triglycerides, and high-density lipoprotein cholesterol on cardiovascular risk factor burden in nondiabetic, obese African American women: implications for the prevalence of metabolic syndrome.

    Science.gov (United States)

    Gaillard, Trudy; Schuster, Dara; Osei, Kwame

    2010-08-01

    Metabolic syndrome (MetS) as defined by the Adult Treatment Panel (ATP) III criteria includes 3 metabolic parameters: serum glucose, triglycerides, and high-density lipoprotein cholesterol (HDL-C) measurements. However, the impact of each of the 3 metabolic parameters on cardiovascular disease (CVD) risk in African American women (AAW) is unknown. Therefore, we investigated CVD risk clusters associated with each of the 3 metabolic components of MetS in adult nondiabetic, overweight/obese AAW. We studied the clinical and metabolic CVD risk factors of 258 AAW (mean age, 42.4 +/- 8.4 years; mean body mass index, 33.4 +/- 8.0 (kg/m(2)). Fasting serum insulin, glucose, and C-peptide levels were obtained in each subject. Waist circumference and systolic and diastolic blood pressure were measured. Insulin sensitivity (Bergman minimal model method) and insulin resistance (homeostasis model assessment) were calculated. We examined the prevalence of MetS and its components associated with each of the 3 metabolic components (ie, serum glucose, HDL-C, and triglycerides) of the MetS as defined by ATP III. Worsening of any of the 3 metabolic parameters was associated with increasing waist circumference but not with age and body mass index nor with insulin, C-peptide, homeostasis model assessment of insulin resistance, and insulin sensitivity. As a group, the prevalence of MetS was 35.5% in our AAW. The prevalence of MetS increased 3-fold from first to third tertiles of serum glucose (14.1% and 42.3%, respectively). Worsening of serum HDL-C from tertiles 3 to 1 was associated with significant increases in the prevalence of MetS (1.2% vs 42.3%, respectively). Comparing first with third tertile of triglycerides, there was no significant increase in MetS in our AAW (7% vs 17%). Contrasting the 3 metabolic components, the prevalence of MetS was higher in the third tertile of glucose (43.2%) and first tertile of HDL-C (42.3%) and least with the third tertile of triglycerides (17%). In

  14. 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...

  15. Improvement of Lipid Profile Is Accompanied by Atheroprotective Alterations in High-Density Lipoprotein Composition Upon Tumor Necrosis Factor Blockade A Prospective Cohort Study in Ankylosing Spondylitis

    NARCIS (Netherlands)

    Eijk, van I.C.; Vries, de M.K.; Levels, J.H.M.; Peters, M.J.L.; Huizer, E.E.; Dijkmans, B.A.C.; Horst - Bruinsma, van der I.E.; Hazenberg, B.P.C.; Stadt, van de R.J.; Wolbink, G.; Nurmohamed, M.T.

    2009-01-01

    Objective. Cardiovascular mortality is increased in ankylosing spondylitis (AS), and inflammation plays an important role. Inflammation deteriorates the lipid profile and alters high-density lipoprotein cholesterol (HDL-c) composition, reflected by increased concentrations of serum amyloid A (SAA)

  16. Impaired suppression of plasma free fatty acids and triglycerides by acute hyperglycaemia-induced hyperinsulinaemia and alterations in high density lipoproteins in essential hypertension

    NARCIS (Netherlands)

    Ligtenberg, JJM; vanTol, A; vanHaeften, TW; Sluiter, WJ; Dullaart, RPF

    1996-01-01

    Objectives. Essential hypertension may be associated with abnormalities in free fatty acids (FFA) and triglyceride metabolism, which could lead to alterations in high density lipoproteins (HDL). Lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) are key

  17. Biominetic High Density Lipoproteins for the Delivery of Therapeutic Oligonucleotides

    Science.gov (United States)

    Tripathy, Sushant

    Advances in nanotechnology have brought about novel inorganic and hybrid nanoparticles with unique physico-chemical properties that make them suitable for a broad range of applications---from nano-circuitry to drug delivery. A significant part of those advancements have led to ground-breaking discoveries that have changed the approaches to formulation of therapeutics against diseases, such as cancer. Now-a-days the focus does not lie solely on finding a candidate small-molecule therapeutic with minimal adverse effects, but researchers are looking up to nanoparticles to improve biodistribution and biocompatibility profile of clinically proven therapeutics. The plethora of conjugation chemistries offered by currently extant inorganic nanoparticles have, in recent years, led to great leaps in the field of biomimicry---a modality that promises high biocompatibility. Further, in the pursuit of highly specific therapeutic molecules, researchers have turned to silencing oligonucleotides and some have already brought together the strengths of nanoparticles and silencing oligonucleotides in search of an efficacious therapy for cancer with minimal adverse effects. This dissertation work focuses on such a biomimetic platform---a gold nanoparticle based high density lipoprotein biomimetic (HDL NP), for the delivery of therapeutic oligonucleotides. The first chapter of this body of work introduces the molecular target of the silencing oligonucleotides---VEGFR2, and its role in the progression of solid tumor cancers. The background information also covers important aspects of natural high density lipoproteins (HDL), especially their innate capacity to bind and deliver exogenous and endogenous silencing oligonucleotides to tissues that express their high affinity receptor SRB1. We subsequently describe the synthesis of the biomimetic HDL NP and its oligonucleotide conjugates, and establish their biocompatibility. Further on, experimental data demonstrate the efficacy of silencing

  18. 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...

  19. 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...

  20. 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...

  1. The High-Density Lipoprotein Puzzle: Why Classic Epidemiology, Genetic Epidemiology, and Clinical Trials Conflict?

    Science.gov (United States)

    Rosenson, Robert S

    2016-05-01

    Classical epidemiology has established the incremental contribution of the high-density lipoprotein (HDL) cholesterol measure in the assessment of atherosclerotic cardiovascular disease risk; yet, genetic epidemiology does not support a causal relationship between HDL cholesterol and the future risk of myocardial infarction. Therapeutic interventions directed toward cholesterol loading of the HDL particle have been based on epidemiological studies that have established HDL cholesterol as a biomarker of atherosclerotic cardiovascular risk. However, therapeutic interventions such as niacin, cholesteryl ester transfer protein inhibitors increase HDL cholesterol in patients treated with statins, but have repeatedly failed to reduce cardiovascular events. Statin therapy interferes with ATP-binding cassette transporter-mediated macrophage cholesterol efflux via miR33 and thus may diminish certain HDL functional properties. Unraveling the HDL puzzle will require continued technical advances in the characterization and quantification of multiple HDL subclasses and their functional properties. Key mechanistic criteria for clinical outcomes trials with HDL-based therapies include formation of HDL subclasses that improve the efficiency of macrophage cholesterol efflux and compositional changes in the proteome and lipidome of the HDL particle that are associated with improved antioxidant and anti-inflammatory properties. These measures require validation in genetic studies and clinical trials of HDL-based therapies on the background of statins. © 2016 American Heart Association, Inc.

  2. Human plasma phospholipid transfer protein increases the antiatherogenic potential of high density lipoproteins in transgenic mice

    NARCIS (Netherlands)

    M.J. van Haperen (Rien); A. van Tol (Arie); P. Vermeulen; M. Jauhiainen; T. van Gent (Teus); P.M. van den Berg (Paul); S. Ehnholm (Sonja); A.W.M. van der Kamp (Arthur); M.P.G. de Crom (Rini); F.G. Grosveld (Frank)

    2000-01-01

    textabstractPlasma phospholipid transfer protein (PLTP) transfers phospholipids between lipoprotein particles and alters high density lipoprotein (HDL) subfraction patterns in vitro, but its physiological function is poorly understood. Transgenic mice that overexpress

  3. 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.

  4. [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.

  5. 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)

  6. 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.

  7. 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.

  8. 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....

  9. The biological properties of iron oxide core high-density lipoprotein in experimental atherosclerosis

    NARCIS (Netherlands)

    Skajaa, Torjus; Cormode, David P.; Jarzyna, Peter A.; Delshad, Amanda; Blachford, Courtney; Barazza, Alessandra; Fisher, Edward A.; Gordon, Ronald E.; Fayad, Zahi A.; Mulder, Willem J. M.

    2011-01-01

    Lipoproteins are a family of plasma nanoparticles responsible for the transportation of lipids throughout the body. High-density lipoprotein (HDL), the smallest of the lipoprotein family, measures 7-13 nm in diameter and consists of a cholesteryl ester and triglyceride core that is covered with a

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

    OpenAIRE

    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 pho...

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. Hydrolysis of phosphatidylcholine by hepatic lipase in discoidal and spheroidal recombinant high-density lipoprotein.

    Science.gov (United States)

    Tansey, J T; Thuren, T Y; Jerome, W G; Hantgan, R R; Grant, K; Waite, M

    1997-10-07

    Hepatic lipase (HL) hydrolysis of phosphatidylcholine (PC) was studied in recombinant high-density lipoprotein particles (r-HDL). r-HDL were made from cholate mixed micelles that contained PC, apo AI, and, in some cases, unesterified cholesterol. r-HDL were characterized using chemical composition, nondenaturing gradient gel electrophoresis, transmission electron microscopy, and dynamic light scattering. The r-HDL were found to be discoidal and in the size range of native HDL. Upon treatment of cholesterol-containing r-HDL with lecithin-cholesterol acyltransferase (LCAT), to form cholesteryl ester, the discoidal r-HDL became spheroidal. The effects of r-HDL morphology and size on HL activity were studied on r-HDL made of palmitoyloleoyl-PC, unesterified cholesterol, cholesteryl ester, and apolipoprotein AI. Spheroidal r-HDL were hydrolyzed at a faster rate than discoidal r-HDL. Protein-poor r-HDL were hydrolyzed by HL at a faster rate than protein rich r-HDL. Unesterified cholesterol had no apparent effect on particle PC hydrolysis. The hydrolysis of different species of PC [dipalmitoyl (DPPC), dioleoyl(DOPC), palmitoylarachidonoyl (PAPC), and palmitoyloleoyl (POPC)] in r-HDL was also investigated. In discoidal r-HDL, we found that POPC >/= DOPC = PAPC/DPPC. However, in LCAT-treated spheroidal r-HDL, POPC = DOPC > PAPC/DPPC. In both discoidal and spheroidal rHDL, DPPC containing r-HDL were not hydrolyzed to a significant extent. Collectively, these studies demonstrate that the physico-chemical properties of particles (such as phospholipid packing and phospholipid acyl composition) play a significant role in hydrolysis of HDL phospholipid by HL and, therefore, in reverse cholesterol transport.

  17. 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

  18. 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)

  19. 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...

  20. Novel association of the R230C variant of the ABCA1 gene with high triglyceride levels and low high-density lipoprotein cholesterol levels in Mexican school-age children with high prevalence of obesity.

    Science.gov (United States)

    Gamboa-Meléndez, Marco Alberto; Galindo-Gómez, Carlos; Juárez-Martínez, Liliana; Gómez, F Enrique; Diaz-Diaz, Eulises; Ávila-Arcos, Marco Antonio; Ávila-Curiel, Abelardo

    2015-08-01

    Metabolic syndrome (MetS) is a disorder that includes a cluster of several risk factors for the development of type 2 diabetes and cardiovascular disease. The R230C variant of the ABCA1 gene has been associated with low HDL-cholesterol in several studies, but its association with MetS in children remains to be determined. The aim of this study was to analyze the association of the R230C variant with MetS and other metabolic traits in school-aged Mexican children. The study was performed in seven urban primary schools in the State of Mexico. Four hundred thirty-two Mexican school-age children 6-13 years old were recruited. MetS was identified using the International Diabetes Federation definition. The R230C variant of the ABCA1 gene was genotyped to seek associations with MetS and other metabolic traits. The prevalence of MetS was 29% in children aged 10-13 years. The R230C variant was not associated with MetS (OR = 1.65; p = 0.139). Furthermore, in the whole population, the R230C variant was associated with low HDL-cholesterol levels (β coefficient = -3.28, p <0.001). Interestingly, in the total population we found a novel association of this variant with high triglyceride levels (β coefficient = 14.34; p = 0.027). We found a new association of the R230C variant of the ABCA1 gene with high triglyceride levels. Our findings also replicate the association of this variant with low HDL-cholesterol levels in Mexican school-age children. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

  1. Sphingomyelin in High-Density Lipoproteins: Structural Role and Biological Function

    Directory of Open Access Journals (Sweden)

    Jesús Osada

    2013-04-01

    Full Text Available High-density lipoprotein (HDL levels are an inverse risk factor for cardiovascular diseases, and sphingomyelin (SM is the second most abundant phospholipid component and the major sphingolipid in HDL. Considering the marked presence of SM, the present review has focused on the current knowledge about this phospholipid by addressing its variable distribution among HDL lipoparticles, how they acquire this phospholipid, and the important role that SM plays in regulating their fluidity and cholesterol efflux from different cells. In addition, plasma enzymes involved in HDL metabolism such as lecithin–cholesterol acyltransferase or phospholipid transfer protein are inhibited by HDL SM content. Likewise, HDL SM levels are influenced by dietary maneuvers (source of protein or fat, drugs (statins or diuretics and modified in diseases such as diabetes, renal failure or Niemann–Pick disease. Furthermore, increased levels of HDL SM have been shown to be an inverse risk factor for coronary heart disease. The complexity of SM species, described using new lipidomic methodologies, and their distribution in different HDL particles under many experimental conditions are promising avenues for further research in the future.

  2. The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

    DEFF Research Database (Denmark)

    Grarup, Niels; Andreasen, Camilla H; Andersen, Mette K

    2008-01-01

    -tolerant control subjects (n = 360). RESULTS: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive...... Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A...... of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped...

  3. Short-Term Red Wine Consumption Promotes Differential Effects on Plasma Levels of High-Density Lipoprotein Cholesterol, Sympathetic Activity, and Endothelial Function in Hypercholesterolemic, Hypertensive, and Healthy Subjects

    Science.gov (United States)

    Andrade, Ana CM; Cesena, Fernando HY; Consolim-Colombo, Fernanda M; Coimbra, Silmara R; Benjó, Alexandre M; Krieger, Eduardo M; da Luz, Protasio Lemos

    2009-01-01

    OBJECTIVES: To compare the metabolic, hemodynamic, autonomic, and endothelial responses to short-term red wine consumption in subjects with hypercholesterolemia or arterial hypertension, and healthy controls. METHODS: Subjects with hypercholesterolemia (n=10) or arterial hypertension (n=9), or healthy controls (n=7) were given red wine (250 mL/night) for 15 days. Analyses were performed before and after red wine intake. RESULTS: Red wine significantly increased the plasma levels of HDL-cholesterol in the controls, but not in the other groups. The effects on hemodynamic measurements were mild, non-significantly more prominent in healthy subjects, and exhibited high interindividual variability. Across all participants, mean blood pressure decreased 7 mmHg (p <0.01) and systemic vascular resistance decreased 7% (p = 0.05). Heart rate and cardiac output did not significantly change in any group. Red wine enhanced muscle sympathetic fibular nerve activity in hypercholesterolemic and hypertensive patients, but not in controls. At baseline, brachial artery flow-mediated dilation was impaired in patients with hypercholesterolemia and arterial hypertension; red wine restored the dilation in the hypercholesterolemic group but not in the hypertensive group. CONCLUSIONS: Red wine elicits different metabolic, autonomic, and endothelial responses among individuals with hypercholesterolemia or arterial hypertension and healthy controls. Our findings highlight the need to consider patient characteristics when evaluating the response to red wine. PMID:19488610

  4. 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 ...

  5. Consuming a hypocaloric high fat low carbohydrate diet for 12 weeks lowers C-reactive protein, and raises serum adiponectin and high density lipoprotein-cholesterol in obese subjects.

    Science.gov (United States)

    Ruth, Megan R; Port, Ava M; Shah, Mitali; Bourland, Ashley C; Istfan, Nawfal W; Nelson, Kerrie P; Gokce, Noyan; Apovian, Caroline M

    2013-12-01

    High fat, low carbohydrate (HFLC) diets have become popular tools for weight management. We sought to determine the effects of a HFLC diet compared to a low fat high carbohydrate (LFHC) diet on the change in weight loss, cardiovascular risk factors and inflammation in subjects with obesity. Obese subjects (29.0-44.6 kg/m2) recruited from Boston Medical Center were randomized to a hypocaloric LFHC (n=26) or HFLC (n=29) diet for 12 weeks. The age range of subjects was 21-62 years. As a percentage of daily calories, the HFLC group consumed 33.5% protein, 56.0% fat and 9.6% carbohydrate and the LFHC group consumed 22.0% protein, 25.0% fat and 55.7% carbohydrate. The change in percent body weight, lean and fat mass, blood pressure, flow mediated dilation, hip:waist ratio, hemoglobin A1C, fasting insulin and glucose, and glucose and insulin response to a 2h oral glucose tolerance test did not differ (P>0.05) between diets after 12 weeks. The HFLC group had greater mean decreases in serum triglyceride (P=0.07), and hs-CRP (P=0.03), and greater mean increases in HDL cholesterol (P=0.004), and total adiponectin (P=0.045) relative to the LFHC. Secreted adipose tissue adiponectin or TNF-α did not differ after weight loss for either diet. Relative to the LFHC group, the HFLC group had greater improvements in blood lipids and systemic inflammation with similar changes in body weight and composition. This small-scale study suggests that HFLC diets may be more beneficial to cardiovascular health and inflammation in free-living obese adults compared to LFHC diets. © 2013.

  6. In vivo regulation of scavenger receptor BI and the selective uptake of high density lipoprotein cholesteryl esters in rat liver parenchymal and Kupffer cells

    NARCIS (Netherlands)

    Fluiter, K.; van der Westhuijzen, D. R.; van Berkel, T. J.

    1998-01-01

    High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake. This selective uptake route forms an important step in the so-called reverse cholesterol transport. Scavenger receptor BI (SR-BI) is the only known HDL

  7. 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

  8. A cross-linking study on the particle species of human plasma high density lipoproteins.

    Science.gov (United States)

    Yachida, Y; Minari, O

    1983-08-01

    The present investigation was on the particle species of human plasma high density lipoprotein (HDL) characterized by the stoichiometry of their apoprotein components. HDL2-1, HDL2-2, HDL3-1, and HDL3-2 isolated from normal human plasma by sequential ultracentrifugal flotation were further subfractionated by Bio Gel A-5m gel chromatography or hydroxyapatite column chromatography, and three distinct subfractions were obtained. Subfraction 1 was obtained from all the HDL fractions and it contained mostly apolipoprotein A-I (A-I). Subfraction 2 was obtained from HDL2-2 and HDL3-1 and it contained A-I and apolipoprotein A-II (A-II) in the molar ratio of one to one, and subfraction 3 from HDL2-2 and HDL3-1 contained A-I and apolipoprotein C (C). Each subfraction was treated with bifunctional cross-linking reagents, and the intraparticle cross-linked products of apolipoproteins were examined by SDS-polyacrylamide gel electrophoresis. The results of the cross-linking studies indicated that the HDL2 fraction consisted mainly of lipoprotein particles of the (A-I)4 type and a few of the (A-I)5, (A-I)2(A-II)2, and (A-I)4(C)2 types, and that the HDL3 fraction consisted mainly of (A-I)2(A-II)2 type particles and a few (A-I)4, (A-I)3, (A-I)2, (A-I), and (A-I)3(C)2 type particles. From the results of analyses of the lipid components in the HDL of each type, it was suggested that the function of the particle species of the (A-I)n type (n = 1--5), which contained more cholesteryl ester than the (A-I)2(A-II)2 type, was concerned mainly with cholesterol metabolism.

  9. High-density lipoprotein is a potential growth factor for adrenocortical cells

    International Nuclear Information System (INIS)

    Murao, Koji; Imachi, Hitomi; Cao, Wenming; Yu, Xiao; Li, Junhua; Yoshida, Kazuya; Ahmed, Rania A.M.; Matsumoto, Kensuke; Nishiuchi, Takamasa; Wong, Norman C.W.; Ishida, Toshihiko

    2006-01-01

    The entry of cholesterol contained within high-density lipoprotein (HDL) into adrenocortical cells is mediated by a human homologue of SR-BI, CD36, and LIMPII Analogous-1 (CLA-1) and thus augmenting their growth. To address the role of CLA-1, we created a mutant mCLA that lacked the C-terminal tail. HDL CE selective uptake by cells carrying the mCLA-1 receptor was fully active and equivalent to those transfected with full-length CLA-1 (fCLA-1). Expression of mCLA inhibited the proliferation of an adrenocortical cell line and the incorporation of [ 3 H]thymidine into the cells. This effect was sensitive to wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). Our transcriptional studies revealed that the inhibitory action of mCLA required the transcriptional factor AP-1 and the effect of HDL on AP-1 activation was also abrogated by wortmannin. These findings raise the possibility that the inhibitors of the effects of HDL may be of therapeutic value for adrenocortical tumor

  10. Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications.

    Science.gov (United States)

    Cho, Kyung-Hyun

    2009-07-31

    High-density lipoprotein (HDL) is a proven biomarker for the monitoring of changes in antioxidant and anti-inflammation capability of body fluids. The beneficial virtues of HDL are highly dependent on its lipids and protein compositions, and their ratios. In normal state, the HDL particle is enriched with lipids and several HDL-associated enzymes, which are responsible for its antioxidant activity. Lower HDL-cholesterol levels (40 mg/dL) have been recognized as an independent risk factor for coronary artery disease, as well as being a known component of metabolic syndrome. Functional and structural changes of HDL have been recognized as factors pivotal to the evaluation of HDL-quality. In this review, I have elected to focus on the functional and structural correlations of HDL and the roles of HDL-associated apolipoproteins and enzymes. Recent clinical applications of HDL have also been reviewed, particularly the therapeutic targeting of HDL metabolism and reconstituted HDL; these techniques represent promising emerging strategies for the treatment of cardiovascular disease, for drug or gene therapy.

  11. 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...

  12. 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...

  13. 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.

  14. High-Density Lipoprotein Function in Exudative Age-Related Macular Degeneration.

    Directory of Open Access Journals (Sweden)

    Laura Pertl

    Full Text Available High-density lipoproteins (HDL have long been implicated in the pathogenesis of age-related macular degeneration (AMD. However, conflicting results have been reported with regard to the associations of AMD with HDL-cholesterol levels. The present study is the first to assess HDL composition and metrics of HDL function in patients with exudative AMD and control patients.Blood samples were collected from 29 patients with exudative AMD and 26 age-matched control patients. Major HDL associated apolipoproteins were determined in apoB-depleted serum by immunoturbidimetry or ELISA, HDL-associated lipids were quantified enzymatically. To get an integrated measure of HDL quantity and quality, we assessed several metrics of HDL function, including cholesterol efflux capacity, anti-oxidative and anti-inflammatory activities using apoB-depleted serum from study participants.In our study, we observed that the HDL associated acute phase protein serum amyloid A (SAA was significantly increased in AMD patients (p<0.01, whereas all other assessed apolipoproteins including ApoA-I, apoA-II, apoC-II, apoC-III and apoE as well as major HDL associated lipids were not altered. HDL efflux capacity, anti-oxidative capacity and arylesterase activity were not different in AMD patients when compared with the control group. The ability of apoB-depleted serum to inhibit monocyte NF-κB expression was significantly improved in AMD patients (mean difference (MD -5.6, p<0.01. Moreover, lipoprotein-associated phospholipase A2 activity, a marker of vascular inflammation, was decreased in AMD subjects (MD -24.1, p<0.01.The investigated metrics of HDL composition and HDL function were not associated with exudative AMD in this study, despite an increased content of HDL associated SAA in AMD patients. Unexpectedly, anti-inflammatory activity of apoB-depleted serum was even increased in our study. Our data suggest that the investigated parameters of serum HDL function showed no

  15. 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

  16. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Drew, Brian G; Duffy, Stephen J; Formosa, Melissa F

    2009-01-01

    BACKGROUND: Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP...

  17. Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform

    NARCIS (Netherlands)

    Cormode, David P.; Skajaa, Torjus; van Schooneveld, Matti M.; Koole, Rolf; Jarzyna, Peter; Lobatto, Mark E.; Calcagno, Claudia; Barazza, Alessandra; Gordon, Ronald E.; Zanzonico, Pat; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2008-01-01

    High density lipoprotein (HDL) is an important natural nanoparticle that may be modified for biomedical imaging purposes. Here we developed a novel technique to create unique multimodality HDL mimicking nanoparticles by incorporation of gold, iron oxide, or quantum dot nanocrystals for computed

  18. Increased Antioxidant Quality Versus Lower Quantity Of High Density Lipoprotein In Benign Prostatic Hyperplasia

    Directory of Open Access Journals (Sweden)

    Aydin Ozgur

    2015-10-01

    Full Text Available Background: Oxidative stress may be involved in the pathogenesis of every human disease. To understand its possible role in benign prostatic hyperplasia (BPH, we measured the overall oxidative status of patients with BPH and the serum activity of the high density lipoprotein (HDL-related antioxidant enzymes paraoxonase 1 (PON1 and arylesterase (ARE.

  19. 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...

  20. Synthetic high-density lipoprotein nanodisks for targeted withalongolide delivery to adrenocortical carcinoma

    Directory of Open Access Journals (Sweden)

    Kuai R

    2017-09-01

    Full Text Available Rui Kuai,1,2,* Chitra Subramanian,3,* Peter T White,3,* Barbara N Timmermann,4 James J Moon,1,2,5 Mark S Cohen,3,6 Anna Schwendeman1,2 1Department of Pharmaceutical Sciences, College of Pharmacy, 2Biointerfaces Institute, University of Michigan, 3Department of Surgery, University of Michigan, Ann Arbor, MI, 4Department of Medicinal Chemistry, University of Kansas, Lawrence, KS, 5Department of Biomedical Engineering, 6Department of Pharmacology, University of Michigan, Ann Arbor, MI, USA *These authors contributed equally to this work Abstract: Adrenocortical carcinoma (ACC is a rare endocrine malignancy and has a 5-year survival rate of <35%. ACC cells require cholesterol for steroid hormone production, and this requirement is met via expression on the cell surface of a high level of SRB1, responsible for the uptake of high-density lipoproteins (HDLs, which carry and transport cholesterol in vivo. Here, we describe how this natural lipid carrier function of SRB1 can be utilized to improve the tumor-targeted delivery of a novel natural product derivative – withalongolide A 4,19,27-triacetate (WGA-TA – which has shown potent antitumor efficacy, but poor aqueous solubility. Our strategy was to use synthetic HDL (sHDL nanodisks, which are effective in tumor-targeted delivery due to their smallness, long circulation half-life, documented safety, and ability to bind to SRB1. In this study, we prepared sHDL nanodisks using an optimized phospholipid composition combined with ApoA1 mimetic peptide (22A, which has previously been tested in clinical trials, to load WGA-TA. Following optimization, WGA-TA nanodisks showed drug encapsulation efficiency of 78%, a narrow particle size distribution (9.81±0.41 nm, discoid shape, and sustained drug release in phosphate buffered saline. WGA-TA-sHDL nanodisks exhibited higher cytotoxicity in the ACC cell line H295R half maximal inhibitory concentration ([IC50] 0.26±0.045 µM than free WGA-TA (IC50 0.492±0

  1. 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

  2. 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.

  3. Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

    Science.gov (United States)

    Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

    2013-01-01

    High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 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.

  5. High-density lipoproteins inhibit urate crystal-induced inflammation in mice

    OpenAIRE

    Scanu Anna; Luisetto Roberto; Oliviero Francesca; Gruaz Lyssia; Sfriso Paolo; Burger Danielle; Punzi Leonardo

    2015-01-01

    Objectives To investigate the effects and mechanisms of action of high density lipoproteins (HDL) in monosodium urate (MSU) crystal induced inflammation—that is gouty inflammation in vivo. Methods Air pouches raised on the backs of mice were injected with MSU crystals or tumour necrosis factor (TNF) in the presence or absence of HDL and/or interleukin (IL) 1 receptor antagonist (IL 1Ra) for 3 h. Leucocyte count and neutrophil percentage in pouch fluids were measured using a haemocytometer an...

  6. 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

  7. High-density lipoprotein apolipoproteins in urine: I. Characterization in normal subjects and in patients with proteinuria.

    Science.gov (United States)

    Gomo, Z A; Henderson, L O; Myrick, J E

    1988-09-01

    A high-resolution two-dimensional electrophoretic method for protein, with silver staining, has been used to characterize and identify urinary high-density-lipoprotein apolipoproteins (HDL-Apos) and their isoforms in healthy subjects and in patients with kidney disease. Analytical techniques based on both molecular mass and ultracentrifugal flotation properties were used to isolate urinary lipoprotein particles with characteristics identical to those of HDL in plasma. HDL-Apos identified in urine of normal subjects and patients with glomerular proteinuria were Apos A-I, A-II, and C. Five isoforms of Apo A-I were present. Immunostaining of electroblotted proteins further confirmed the presence of HDL-Apos in urine. Creatinine clearance rate was decreased in the patients with proteinuria, and ranged from 32.5 to 40 mL/min. Concentrations of cholesterol and triglycerides in serum were greater in the patients' group, whereas mean HDL-cholesterol (0.68, SD 0.10 mmol/L) and Apo A-I (0.953, SD 0.095 g/L) were significantly (each P less than 0.01) lower. Results of this study suggest that measurement of urinary Apo A-I will reflect excretion of HDL in urine.

  8. Patterns and trends of potentially inappropriate high-density lipoprotein cholesterol testing in Australian adults at high risk of cardiovascular disease from 2008 to 2014: analysis of linked individual patient data from the Australian Medicare Benefits Schedule and Pharmaceutical Benefits Scheme.

    Science.gov (United States)

    Hajati, Farshid; Atlantis, Evan; Bell, Katy J L; Girosi, Federico

    2018-03-08

    We examine the extent to which the adult Australian population on lipid-lowering medications receives the level of high-density lipoprotein cholesterol (HDL-C) testing recommended by national guidelines. We analysed records from 7 years (2008-2014) of the 10% publicly available sample of deidentified, individual level, linked Medicare Benefits Schedule (MBS) and Pharmaceutical Benefits Scheme (PBS) electronic databases of Australia. The PBS data were used to identify individuals on stable prescriptions of lipid-lowering treatment. The MBS data were used to estimate the annual frequency of HDL-C testing. We developed a methodology to address the issue of 'episode coning' in the MBS data, which causes an undercounting of pathology tests. We used a published figure on the proportion of unreported HDL-C tests to correct for the undercounting and estimate the probability that an HDL-C test was performed. We judged appropriateness of testing frequency by comparing the HDL-C testing rate to guidelines' recommendations of annual testing for people at high risk for cardiovascular disease. We estimated that approximately 49% of the population on stable lipid-lowering treatment did not receive any HDL-C test in a given year. We also found that approximately 19% of the same population received two or more HDL-C tests within the year. These levels of underutilisation and overutilisation have been changing at an average rate of 2% and -4% a year, respectively, since 2009. The yearly expenditure associated with test overutilisation was approximately $A4.3 million during the study period, while the cost averted because of test underutilisation was approximately $A11.3 million a year. We found that approximately half of Australians on stable lipid-lowering treatment may be having fewer HDL-C testing than recommended by national guidelines, while nearly one-fifth are having more tests than recommended. © Article author(s) (or their employer(s) unless otherwise stated in the text

  9. 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

  10. Non-leaky vesiculation of large unilamellar vesicles (LUV) induced by plasma high density lipoproteins (HDL): Detection by HPLC

    International Nuclear Information System (INIS)

    Tischler, U.; Rueckert, D.S.; Schubert, R.; Jaroni, H.W.; Schmidt, K.H.

    1989-01-01

    Interaction of large unilamellar phosphatidylcholine vesicles (LUV, 75nm) and plasma high density lipoproteins (HDL) resulted in a non-leaky vesiculation of LUV. This vesiculation was detected by a HPLC-system consisting of a combination of three TSK-gel columns (6000PW, 5000PW, 3000SW). With increasing incubation time liposomal [ 14 C]PC, entrapped [ 3 H]inulin, and apoprotein of HDL origin decreased. The decrease was accompanied by a formation of new particles, consisting of liposomal PC and apoprotein. These particles also enclosed [3H]inulin, reflecting a hydrophilic inner space. The formation of the particles reached a maximum after one day of incubation. Retention time was 21 minutes for LUV, 28 minutes for the new particles, and 36 minutes for HDL. In vesicles with membranes consisting of phosphatidylcholine and 30% cholesterol no interactions were observed

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. How Well Does BODIPY-Cholesteryl Ester Mimic Unlabeled Cholesteryl Esters in High Density Lipoprotein Particles?

    DEFF Research Database (Denmark)

    Karilainen, Topi; Vuorela, Timo; Vattulainen, Ilpo

    2015-01-01

    We compare the behavior of unlabeled and BODIPY-labeled cholesteryl ester (CE) in high density lipoprotein by atomistic molecular dynamics simulations. We find through replica exchange umbrella sampling and unbiased molecular dynamics simulations that BODIPY labeling has no significant effect...... on the partitioning of CE between HDL and the water phase. However, BODIPY-CE was observed to diffuse more slowly and locate itself closer to the HDL-water interface than CE due to the BODIPY probe that is constrained to the surface region, and because the CE body in BODIPY-CE prefers to align itself away from...... the HDL surface. The implications as to the suitability of BODIPY to explore lipoprotein properties are discussed....

  16. Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.

    Science.gov (United States)

    Saïdi, Y; Sich, D; Camproux, A; Egloff, M; Federspiel, M C; Gautier, V; Raisonnier, A; Turpin, G; Beucler, I

    1999-01-01

    We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.

  17. Anion exchange HPLC isolation of high-density lipoprotein (HDL and on-line estimation of proinflammatory HDL.

    Directory of Open Access Journals (Sweden)

    Xiang Ji

    Full Text Available Proinflammatory high-density lipoprotein (p-HDL is a biomarker of cardiovascular disease. Sickle cell disease (SCD is characterized by chronic states of oxidative stress that many consider to play a role in forming p-HDL. To measure p-HDL, apolipoprotein (apo B containing lipoproteins are precipitated. Supernatant HDL is incubated with an oxidant/LDL or an oxidant alone and rates of HDL oxidation monitored with dichlorofluorescein (DCFH. Although apoB precipitation is convenient for isolating HDL, the resulting supernatant matrix likely influences HDL oxidation. To determine effects of supernatants on p-HDL measurements we purified HDL from plasma from SCD subjects by anion exchange (AE chromatography, determined its rate of oxidation relative to supernatant HDL. SCD decreased total cholesterol but not triglycerides or HDL and increased cell-free (cf hemoglobin (Hb and xanthine oxidase (XO. HDL isolated by AE-HPLC had lower p-HDL levels than HDL in supernatants after apoB precipitation. XO+xanthine (X and cf Hb accelerated purified HDL oxidation. Although the plate and AE-HPLC assays both showed p-HDL directly correlated with cf-Hb in SCD plasma, the plate assay yielded p-HDL data that was influenced more by cf-Hb than AE-HPLC generated p-HDL data. The AE-HPLC p-HDL assay reduces the influence of the supernatants and shows that SCD increases p-HDL.

  18. Anion exchange HPLC isolation of high-density lipoprotein (HDL) and on-line estimation of proinflammatory HDL.

    Science.gov (United States)

    Ji, Xiang; Xu, Hao; Zhang, Hao; Hillery, Cheryl A; Gao, Hai-Qing; Pritchard, Kirkwood A

    2014-01-01

    Proinflammatory high-density lipoprotein (p-HDL) is a biomarker of cardiovascular disease. Sickle cell disease (SCD) is characterized by chronic states of oxidative stress that many consider to play a role in forming p-HDL. To measure p-HDL, apolipoprotein (apo) B containing lipoproteins are precipitated. Supernatant HDL is incubated with an oxidant/LDL or an oxidant alone and rates of HDL oxidation monitored with dichlorofluorescein (DCFH). Although apoB precipitation is convenient for isolating HDL, the resulting supernatant matrix likely influences HDL oxidation. To determine effects of supernatants on p-HDL measurements we purified HDL from plasma from SCD subjects by anion exchange (AE) chromatography, determined its rate of oxidation relative to supernatant HDL. SCD decreased total cholesterol but not triglycerides or HDL and increased cell-free (cf) hemoglobin (Hb) and xanthine oxidase (XO). HDL isolated by AE-HPLC had lower p-HDL levels than HDL in supernatants after apoB precipitation. XO+xanthine (X) and cf Hb accelerated purified HDL oxidation. Although the plate and AE-HPLC assays both showed p-HDL directly correlated with cf-Hb in SCD plasma, the plate assay yielded p-HDL data that was influenced more by cf-Hb than AE-HPLC generated p-HDL data. The AE-HPLC p-HDL assay reduces the influence of the supernatants and shows that SCD increases p-HDL.

  19. Novel changes in discoidal high density lipoprotein morphology: a molecular dynamics study.

    Science.gov (United States)

    Catte, Andrea; Patterson, James C; Jones, Martin K; Jerome, W Gray; Bashtovyy, Denys; Su, Zhengchang; Gu, Feifei; Chen, Jianguo; Aliste, Marcela P; Harvey, Stephen C; Li, Ling; Weinstein, Gilbert; Segrest, Jere P

    2006-06-15

    ApoA-I is a uniquely flexible lipid-scavenging protein capable of incorporating phospholipids into stable particles. Here we report molecular dynamics simulations on a series of progressively smaller discoidal high density lipoprotein particles produced by incremental removal of palmitoyloleoylphosphatidylcholine via four different pathways. The starting model contained 160 palmitoyloleoylphosphatidylcholines and a belt of two antiparallel amphipathic helical lipid-associating domains of apolipoprotein (apo) A-I. The results are particularly compelling. After a few nanoseconds of molecular dynamics simulation, independent of the starting particle and method of size reduction, all simulated double belts of the four lipidated apoA-I particles have helical domains that impressively approximate the x-ray crystal structure of lipid-free apoA-I, particularly between residues 88 and 186. These results provide atomic resolution models for two of the particles produced by in vitro reconstitution of nascent high density lipoprotein particles. These particles, measuring 95 angstroms and 78 angstroms by nondenaturing gradient gel electrophoresis, correspond in composition and in size/shape (by negative stain electron microscopy) to the simulated particles with molar ratios of 100:2 and 50:2, respectively. The lipids of the 100:2 particle family form minimal surfaces at their monolayer-monolayer interface, whereas the 50:2 particle family displays a lipid pocket capable of binding a dynamic range of phospholipid molecules.

  20. Comparative studies of vertebrate scavenger receptor class B type 1: a high-density lipoprotein binding protein

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    Holmes RS

    2012-06-01

    Full Text Available Roger S Holmes,1,2 Laura A Cox11Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA; 2School of Biomolecular and Physical Sciences, Griffith University, Nathan, Queensland, AustraliaAbstract: Scavenger receptor class B type 1 protein (SCARB1 plays an essential role in cholesterol homeostasis and functions in binding high density lipoprotein cholesterol (HDL in liver and other tissues of the body. SCARB1 also functions in lymphocyte homeostasis and in the uptake of hepatitis C virus (HCV by the liver. A genetic deficiency of this protein results in autoimmune disorders and significant changes in blood cholesterol phenotype. Comparative SCARB1 amino acid sequences and structures and SCARB1 gene locations were examined using data from several vertebrate genome projects. Vertebrate SCARB1 sequences shared 50%–99% identity as compared with 28%–31% sequence identities with other CD36-like superfamily members, ie, SCARB2 and SCARB3 (also called CD36. At least eight N-glycosylation sites were conserved among most of the vertebrate SCARB1 proteins examined. Sequence alignments, key amino acid residues, and conserved predicted secondary structures were also studied, including: cytoplasmic, transmembrane, and exoplasmic sequences; conserved N-terminal and C-terminal transmembrane glycines which participate in oligomer formation; conserved cystine disulfides and a free SH residue which participates in lipid transport; carboxyl terminal PDZ-binding domain sequences (Ala507-Arg/Lys508-Leu509; and 30 conserved proline and 18 conserved glycine residues, which may contribute to short loop formation within the exoplasmic HDL-binding sequence. Vertebrate SCARB1 genes usually contained 12 coding exons. The human SCARB1 gene contained CpG islands, micro RNA binding sites, and several transcription factor binding sites (including PPARG which may contribute to the high level (13.7 times

  1. 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)

  2. High-density Lipoproteins and Apolipoprotein A-I: Potential New Players in the Prevention and Treatment of Lung Disease

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Gordon

    2016-09-01

    Full Text Available Apolipoprotein A-I (apoA-I and high-density lipoproteins (HDL mediate reverse cholesterol transport out of cells. Furthermore, HDL has additional protective functions, which include anti-oxidative, anti-inflammatory, anti-apoptotic, and vasoprotective effects. In contrast, HDL can become dysfunctional with a reduction in both cholesterol efflux and anti-inflammatory properties in the setting of disease or the acute phase response. These paradigms are increasingly being recognized to be active in the pulmonary system, where apoA-I and HDL have protective effects in normal lung health, as well as in a variety of disease states, including acute lung injury, asthma, chronic obstructive pulmonary disease, lung cancer, pulmonary arterial hypertension, pulmonary fibrosis, and viral pneumonia. Similar to observations in cardiovascular disease, however, HDL may become dysfunctional and contribute to disease pathogenesis in respiratory disorders. Furthermore, synthetic apoA-I mimetic peptides have been shown to have protective effects in animal models of acute lung injury, asthma, pulmonary hypertension, and influenza pneumonia. These findings provide evidence to support the concept that apoA-I mimetic peptides might be developed into a new treatment that can either prevent or attenuate the manifestations of lung diseases, such as asthma. Thus, the lung is positioned to take a page from the cardiovascular disease playbook and utilize the protective properties of HDL and apoA-I as a novel therapeutic approach.

  3. 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

  4. High-density lipoproteins potentiate α1-antitrypsin therapy in elastase-induced pulmonary emphysema.

    Science.gov (United States)

    Moreno, Juan-Antonio; Ortega-Gomez, Almudena; Rubio-Navarro, Alfonso; Louedec, Liliane; Ho-Tin-Noé, Benoit; Caligiuri, Giuseppina; Nicoletti, Antonino; Levoye, Angelique; Plantier, Laurent; Meilhac, Olivier

    2014-10-01

    Several studies report that high-density lipoproteins (HDLs) can carry α1-antitrypsin (AAT; an elastase inhibitor). We aimed to determine whether injection of exogenous HDL, enriched or not in AAT, may have protective effects against pulmonary emphysema. After tracheal instillation of saline or elastase, mice were randomly treated intravenously with saline, human plasma HDL (75 mg apolipoprotein A1/kg), HDL-AAT (75 mg apolipoprotein A1-3.75 mg AAT/kg), or AAT alone (3.75 mg/kg) at 2, 24, 48, and 72 hours. We have shown that HDL-AAT reached the lung and prevented the development of pulmonary emphysema by 59.3% at 3 weeks (alveoli mean chord length, 22.9 ± 2.8 μm versus 30.7 ± 4.5 μm; P pulmonary emphysema than AAT alone, and may represent a significant development for the management of emphysema associated with AAT deficiency.

  5. The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications

    Directory of Open Access Journals (Sweden)

    Nathan K. P. Wong

    2018-06-01

    Full Text Available Almost 600 million people are predicted to have diabetes mellitus (DM by 2035. Diabetic patients suffer from increased rates of microvascular and macrovascular complications, associated with dyslipidaemia, impaired angiogenic responses to ischaemia, accelerated atherosclerosis, and inflammation. Despite recent treatment advances, many diabetic patients remain refractory to current approaches, highlighting the need for alternative agents. There is emerging evidence that high-density lipoproteins (HDL are able to rescue diabetes-related vascular complications through diverse mechanisms. Such protective functions of HDL, however, can be rendered dysfunctional within the pathological milieu of DM, triggering the development of vascular complications. HDL-modifying therapies remain controversial as many have had limited benefits on cardiovascular risk, although more recent trials are showing promise. This review will discuss the latest data from epidemiological, clinical, and pre-clinical studies demonstrating various roles for HDL in diabetes and its vascular complications that have the potential to facilitate its successful translation.

  6. Trypanosome lytic factor, an antimicrobial high-density lipoprotein, ameliorates Leishmania infection.

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    Marie Samanovic

    2009-01-01

    Full Text Available Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system.

  7. 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...

  8. Serum Paraoxonase 1 Activity Is Associated with Fatty Acid Composition of High Density Lipoprotein

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    Maryam Boshtam

    2013-01-01

    Full Text Available Introduction. Cardioprotective effect of high density lipoprotein (HDL is, in part, dependent on its related enzyme, paraoxonase 1 (PON1. Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. Methods. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Results. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA. PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω6 fatty acids of HDL. Conclusion. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

  9. Serum paraoxonase 1 activity is associated with fatty acid composition of high density lipoprotein.

    Science.gov (United States)

    Boshtam, Maryam; Razavi, Amirnader Emami; Pourfarzam, Morteza; Ani, Mohsen; Naderi, Gholam Ali; Basati, Gholam; Mansourian, Marjan; Dinani, Narges Jafari; Asgary, Seddigheh; Abdi, Soheila

    2013-01-01

    Cardioprotective effect of high density lipoprotein (HDL) is, in part, dependent on its related enzyme, paraoxonase 1 (PON1). Fatty acid composition of HDL could affect its size and structure. On the other hand, PON1 activity is directly related to the structure of HDL. This study was designed to investigate the association between serum PON1 activity and fatty acid composition of HDL in healthy men. One hundred and forty healthy men participated in this research. HDL was separated by sequential ultracentrifugation, and its fatty acid composition was analyzed by gas chromatography. PON1 activity was measured spectrophotometrically using paraxon as substrate. Serum PON1 activity was directly correlated with the amount of stearic acid and dihomo-gamma-linolenic acid (DGLA). PON1/HDL-C was directly correlated with the amount of miristic acid, stearic acid, and DGLA and was inversely correlated with total amount of ω 6 fatty acids of HDL. The fatty acid composition of HDL could affect the activity of its associated enzyme, PON1. As dietary fats are the major determinants of serum lipids and lipoprotein composition, consuming some special dietary fatty acids may improve the activity of PON1 and thereby have beneficial effects on health.

  10. High-density lipoprotein-like particle formation of Synuclein variants.

    Science.gov (United States)

    Eichmann, Cédric; Kumari, Pratibha; Riek, Roland

    2017-01-01

    α-Synuclein (α-Syn) is an intrinsically disordered protein in solution whose fibrillar aggregates are the hallmark of Parkinson's disease (PD). Although the specific function of α-Syn is still unclear, its high structural plasticity is key for the interactions of α-Syn with biological membranes. Recently, it has been observed that α-Syn is able to form high-density lipoprotein-like (HDL-like) particles that are reminiscent of self-assembling phospholipid bilayer nanodiscs. Here, we extended our preparation method for the production of α-Syn lipoprotein particles to the β- and γ-Syn variants, and the PD-related familial α-Syn mutants. We show that all human Syns can form stable and homogeneous populations of HDL-like particles with distinct morphologies. Our results characterize the impact of the individual Syns on the formation capacity of these particles and indicate that Syn HDL-like particles are neither causing toxicity nor a toxicity-related loss of α-Syn in PD. © 2016 Federation of European Biochemical Societies.

  11. Expression of human apolipoprotein A-I epitopes in high density lipoproteins and in serum

    International Nuclear Information System (INIS)

    Marcel, Y.L.; Jewer, D.; Vezina, C.; Milthorp, P.; Weech, P.K.

    1987-01-01

    The expression and immunoreactivity of apolipoprotein (apo) A-I epitopes in high density lipoproteins (HDL) and serum has been investigated using two series of monoclonal antibodies (Mabs) which have been described elsewhere. Series 1 Mabs, identified as 3D4, 6B8, and 5G6, were obtained by immunization and screening with apoA-I, and series 2 Mabs, identified as 2F1, 4H1, 3G10, 4F7, and 5F6, were obtained by immunization and screening with HDL. These Mabs were characterized with respect to their binding to HDL particles in solution. In series 2 Mabs, 2F1, 3G10, and 4F7, which react with apoA-I CNBr-fragments 1 and 2, could precipitate 100% of 125 I-labeled HDL, while 4H1 and 5F6, which react with CNBr fragments 1 and 3, precipitated 90 and 60% of 125 I-labeled HDL, respectively. Therefore, three distinct epitopes mapped to CNBr fragments 1 and 2 have been identified which are expressed on all HDL particles, indicating that several antigenic do mains exist on apoA-I which have the same conformation on all apoA-I-containing lipoproteins. The Mabs reacting at these sites have significantly higher affinity constants for 125 I-labeled HDL than those that failed to precipitate 100% of HDL. This suggests that the high affinity Mabs react with apoA-I epitopes that are both expressed on all lipoproteins and located in thermo-dynamically stable regions of the molecules. All Mabs from series 1 precipitated 35% or less of 125 I-labeled HDL prepared from freshly collected serum, but the proportion of HDL particles expressing the epitopes for these Mabs doubled or more upon serum storage at 4 degrees C. The time course of the alteration of apoA-I antigen in vitro was measured in three normolipemic donors

  12. 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

  13. TOTAL CHOLESTEROL, HIGH DENSITY LIPOPROTEINS (HDL AND CORTISOL PLASMA LEVELS, AND THEIR BIORHYTMICITY, IN 24 HOURS, THROUGHOUT YEAR, IN IDEAL-POLWARTH RAMS NÍVEIS PLASMÁTICOS DE COLESTEROL TOTAL, LIPOPROTEÍNAS DE ALTA DENSIDADE (HDL E CORTISOL, E SUA BIORRITMICIDADE, EM CARNEIROS IDEAL-POLWARTH

    Directory of Open Access Journals (Sweden)

    Alcides de Amorim Ramos

    2006-12-01

    Full Text Available To evaluate the mean plasma concentrations of total cholesterol (TC, high density lipoproteins (HDL and cortisol, blood samples were collected of five Ideal-Polwarth rams, maintained at 22?53’S latitude, in semi-confinement, every two months throughout the year, by 24h period, with 2-hour intervals between colects. The TC, changed 40.70?1,11mg/dL (April and 61.48?1,11mg/dL (December, between months, while HDL changed 22.16?0.23mg/dL (December as 33.40?0.23mg/dL (February, but not make evident a circannual rhythm in this levels. The TC presented the lowest value at 16:30h (50.40?1.57mg/dL and the highest value at 8:30h collect (54.67?1.57mg/dL; the HDL lowest level was at 10:30h (27.04?0.33mg/dL and the highest level also at 8:30h collect (28.49?0.33mg/dL, however without permit circadian rhythm determination in your plasma concentrations. Similarly, the cortisol plasma concentrations, between collect months, presents variable, however without demonstrate circadian rhythm in this hormone secretion. In relation to different collection’s moments, throughout months, it wasn’t possible to define, by statistical analysis, a circadian rhythm of cortisol secretion. KEY WORDS: Ovine, adrenal hormone, biochemistry metabolites, circadian rhythm. Visando avaliar as concentrações médias de colesterol total (CT, lipoproteínas de alta densidade (HDL e cortisol plasmáticos, foram colhidas amostras de sangue de cinco carneiros Ideal-Polwarth, alocados em latitude 22°53’S, em regime de semiconfinamento, a cada dois meses, ao longo de um ano, com as colheitas em um período de 24 horas, e intervalos de duas horas entre elas. O CT oscilou entre 40,70±1,11mg/dL (abril e 61,48±1,11mg/dL (dezembro, entre os meses, enquanto HDL variou de 22,16±0,23mg/dL (dezembro a 33,40±0,23mg/dL (fevereiro, mas não evidenciando um ritmo circanual em seus níveis. O CT apresentou seu valor mínimo na colheita das 16h30min (50,40±1,57mg/dL e o máximo às 8h30min

  14. Association of High Density Lipoprotein with Platelet to Lymphocyte and Neutrophil to Lymphocyte Ratios in Coronary Artery Disease Patients

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    Jayesh H. Prajapati

    2014-01-01

    Full Text Available Background. We aimed to evaluate a relationship between platelet-lymphocyte ratio (PLR and neutrophil-lymphocyte ratio (NLR with high density lipoprotein (HDL cholesterol levels in coronary artery disease (CAD patients. Methods. A total of 354 patients with angiographically confirmed coronary blockages were enrolled in the study. Hematological indices and lipid profiling data of all the patients were collected. Results. We have observed significant association between HDL and PLR (P=0.008 and NLR (P=0.009; however no significant relationship was obtained with HDL and isolated platelet (P=0.488, neutrophil (P=0.407, and lymphocyte (P=0.952 counts in CAD patients. The association was subjected to gender specific variation as in males PLR (P=0.024 and NLR (P=0.03 were highly elevated in low HDL patients, whereas in females the elevation could not reach the statistically significant level. The PLR (217.47 versus 190.3; P=0.01 and NLR (6.33 versus 5.10; P=0.01 were significantly higher among the patients with acute coronary syndrome. In young patients the PLR (P=0.007 and NLR (P=0.001 were inversely associated with HDL, whereas in older population only NLR (P=0.05 had showed a significant association. Conclusion. We conclude that PLR and NLR are significantly elevated in CAD patients having low HDL levels.

  15. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL

    International Nuclear Information System (INIS)

    Golay, A.; Zech, L.; Shi, M.Z.; Chiou, Y.A.; Reaven, G.M.; Chen, Y.D.

    1987-01-01

    High density lipoprotein (HDL) kinetics were studied by injecting [ 3 H]apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster [0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001] and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients

  16. Lipoprotein receptors in copper-deficient rats: in vitro binding of high-density lipoprotein subfractions to liver membranes

    International Nuclear Information System (INIS)

    Hassel, C.A.

    1986-01-01

    Three studies were conducted to determine whether the elevated plasma and HDL cholesterol levels observed in copper-deficient rats could be explained by the interaction of 125 I-HDL subfractions with liver membrane preparations in vitro. Rats from all studies were randomly divided into two dietary treatments, copper-deficient and adequate (0.7 mg and 8.0 mg Cukg diet, respectively). Total binding data and computer derived estimates (K/sub d/ and B/sub max/) were used to compare differences between treatments. Binding data from all experiments conformed to a one-site model. In all cases, binding was saturable and EDTA and pronase insensitive. Treatment differences were observed in Study I ( 125 I-apo E-free HDL binding to crude liver membranes). Significantly lower total binding and B/sub max/ were observed when lipoproteins and membranes from copper-deficient animals were used in the assay. Competition experiments from Studies II and III demonstrate that the different HDL subfractions competed effectively with one another for binding sites, indicating that apo E is not a determinant in binding of rat 125 I-HDL subfractions to purified liver plasma membranes

  17. Metabolism of triglyceride-rich nascent rat hepatic high density lipoproteins

    International Nuclear Information System (INIS)

    Winkler, K.E.; Marsh, J.B.

    1989-01-01

    Nascent high density lipoprotein (HDL) and nascent very low density lipoprotein (VLDL) were isolated from rat livers that had been perfused with [3H]glycerol to label the triglyceride. When injected into intact rats, the labeled HDL-triglyceride disappeared as rapidly as the VLDL-triglyceride, with only 10% of the injected label remaining in the plasma after 30 min. The protein moiety of nascent HDL was labeled with [35S]methionine in a similar fashion and the labeled nascent HDL was separated into nonretained (NR) and retained (R) fractions by heparin-Sepharose affinity chromatography. When injected into rats, 55% of the injected label in nascent fraction NR and 72% of that in nascent fraction R was recovered from plasma at 30 min, compared to only 10% of the triglyceride label from unfractionated nascent HDL, indicating dissociation of triglyceride and apolipoprotein clearance. The plasma decay curves for both triglyceride and protein were biexponential. By 5 min, 15% of the 35S label remaining in plasma represented apoE and apoC that had been transferred from nascent HDL fractions NR and R to the d less than 1.063 g/ml fraction of plasma. Plasma HDL was labeled in vivo with [35S]methionine, separated into fractions NR and R, and the clearance of the two plasma HDL fractions was compared with that of the corresponding nascent HDL fractions. Except for a faster rate of removal of the nascent HDL fractions during the first 5 min, the serum decay curves were very similar

  18. One precursor, three apolipoproteins: the relationship between two crustacean lipoproteins, the large discoidal lipoprotein and the high density lipoprotein/β-glucan binding protein.

    Science.gov (United States)

    Stieb, Stefanie; Roth, Ziv; Dal Magro, Christina; Fischer, Sabine; Butz, Eric; Sagi, Amir; Khalaila, Isam; Lieb, Bernhard; Schenk, Sven; Hoeger, Ulrich

    2014-12-01

    The novel discoidal lipoprotein (dLp) recently detected in the crayfish, differs from other crustacean lipoproteins in its large size, apoprotein composition and high lipid binding capacity, We identified the dLp sequence by transcriptome analyses of the hepatopancreas and mass spectrometry. Further de novo assembly of the NGS data followed by BLAST searches using the sequence of the high density lipoprotein/1-glucan binding protein (HDL-BGBP) of Astacus leptodactylus as query revealed a putative precursor molecule with an open reading frame of 14.7 kb and a deduced primary structure of 4889 amino acids. The presence of an N-terminal lipid bind- ing domain and a DUF 1943 domain suggests the relationship with the large lipid transfer proteins. Two-putative dibasic furin cleavage sites were identified bordering the sequence of the HDL-BGBP. When subjected to mass spectroscopic analyses, tryptic peptides of the large apoprotein of dLp matched the N-terminal part of the precursor, while the peptides obtained for its small apoprotein matched the C-terminal part. Repeating the analysis in the prawn Macrobrachium rosenbergii revealed a similar protein with identical domain architecture suggesting that our findings do not represent an isolated instance. Our results indicate that the above three apolipoproteins (i.e HDL-BGBP and both the large and the small subunit of dLp) are translated as a large precursor. Cleavage at the furin type sites releases two subunits forming a heterodimeric dLP particle, while the remaining part forms an HDL-BGBP whose relationship with other lipoproteins as well as specific functions are yet to be elucidated.

  19. 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

  20. 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

  1. Secreted Progranulin Is a Homodimer and Is Not a Component of High Density Lipoproteins (HDL)*

    Science.gov (United States)

    Nguyen, Andrew D.; Nguyen, Thi A.; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C.; Davidson, W. Sean; Farese, Robert V.

    2013-01-01

    Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ∼85 kDa by SDS-PAGE, it elutes in fractions corresponding to ∼170–180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (∼180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ∼180–190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDL either by ultracentrifugation or by lipid binding assays. We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL. PMID:23364791

  2. Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL).

    Science.gov (United States)

    Nguyen, Andrew D; Nguyen, Thi A; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C; Davidson, W Sean; Farese, Robert V

    2013-03-22

    Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ∼85 kDa by SDS-PAGE, it elutes in fractions corresponding to ∼170-180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (∼180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ∼180-190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDL either by ultracentrifugation or by lipid binding assays. We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL.

  3. Intercorrelations among plasma high density lipoprotein, obesity and triglycerides in a normal population.

    Science.gov (United States)

    Albrink, M J; Krauss, R M; Lindgrem, F T; von der Groeben, J; Pan, S; Wood, P D

    1980-09-01

    The interrelationships among fatness measures, plasma triglycerides and high density lipoproteins (HDL) were examined in 131 normal adult subjects: 38 men aged 27-46, 40 men aged 47-66, 29 women aged 27-46 and 24 women aged 47-66. None of the women were taking estrogens or oral contraceptive medication. The HDL concentration was subdivided into HDL2b, HDL2a and HDL3 by a computerized fitting of the total schlieren pattern to reference schlieren patterns. Anthropometric measures employed included skinfolds at 3 sites. 2 weight/height indices and 2 girth measurements. A high correlation was found among the various fatness measures. These measures were negatively correlated with total HDL, reflecting the negative correlation between fatness measures and HDL2 (as the sum of HDL2a and 2b). Fatness measures showed no relationship to HDL3. There was also an inverse correlation between triglyceride concentration and HDL2. No particular fatness measure was better than any other for demonstrating the inverse correlation with HDL but multiple correlations using all of the measures of obesity improved the correlations. Partial correlations controlling for fatness did not reduce any of the significant correlations between triglycerides and HDL2 to insignificance. The weak correlation between fatness and triglycerides was reduced to insignificance when controlled for HDL2.

  4. Long term stability of paraoxonase-1 and high-density lipoprotein in human serum

    Directory of Open Access Journals (Sweden)

    Beekhof Piet K

    2012-05-01

    Full Text Available Abstract Background Paraoxonase-1 (PON1 is an enzyme with numerous functions and receives an increasing interest in clinical and epidemiological studies. Sometimes samples are stored for longer periods at a certain temperature. Therefore the stability of PON1 activity must be checked and retained upon storage for longer periods. Results In this study the stability of PON1 activity has been tested in human serum samples during storage up to 12 months at 3 commonly used temperatures, -20°C, -70°C and −196°C. It was found that the stability of the PON1 activity is constant during 12 months of storage at −70°C and −196°C. Storage at −20°C resulted in a small but statistically significant decrease after 6 months to about 94% of its original value. Nonetheless, the rank order between the samples at T = 0 and 12 months remained the same. The same temperature dependence was found for the associated high-density lipoprotein. Conclusions It can be concluded that −70°C is the right temperature for storage to maintain the PON1 activity for at least one year. Storage at a lower temperature in liquid nitrogen (−196°C is not necessary.

  5. A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

    Science.gov (United States)

    Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2014-01-01

    Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

  6. 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.

  7. 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

  8. Reconstituted high-density lipoprotein infusion modulates fatty acid metabolism in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Drew, BG; Carey, AL; Natoli, AK

    2011-01-01

    We recently demonstrated that reconstituted high-density lipoprotein (rHDL) modulates glucose metabolism in humans via both AMP-activated protein kinase (AMPK) in muscle and by increasing plasma insulin. Given the key roles of both AMPK and insulin in fatty acid metabolism, the current study inve...

  9. The complex fate in plasma of gadolinium incorporated into high-density lipoproteins used for magnetic imaging of atherosclerotic plaques

    NARCIS (Netherlands)

    Barazza, Alessandra; Blachford, Courtney; Even-Or, Orli; Joaquin, Victor A.; Briley-Saebo, Karen C.; Chen, Wei; Jiang, Xian-Cheng; Mulder, Willem J. M.; Cormode, David P.; Fayad, Zahi A.; Fisher, Edward A.

    2013-01-01

    We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL,

  10. 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)

  11. 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,.

  12. 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.

  13. 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

  14. Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

    Science.gov (United States)

    Gebhard, C; Maafi, F; Stähli, B E; Bonnefoy, A; Gebhard, C E; Nachar, W; de Oliveira Moraes, A Benjamim; Mecteau, M; Mihalache-Avram, T; Lavoie, V; Kernaleguen, A E; Shi, Y; Busseuil, D; Chabot-Blanchet, M; Perrault, L P; Rhainds, D; Rhéaume, E; Tardif, J C

    2018-02-01

     Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown.  We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS ( n  = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls ( p  AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p  AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p  AVS ( r  = -0.3, p  = 0.045).  Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS. Schattauer GmbH Stuttgart.

  15. WDR1 and CLNK gene polymorphisms correlate with serum glucose and high-density lipoprotein levels in Tibetan gout patients.

    Science.gov (United States)

    Lan, Bing; Chen, Peng; Jiri, Mutu; He, Na; Feng, Tian; Liu, Kai; Jin, Tianbo; Kang, Longli

    2016-03-01

    Current evidence suggests heredity and metabolic syndrome contributes to gout progression. Specifically, the WDR1 and CLNK genes may play a role in gout progression in European ancestry populations. However, no studies have focused on Chinese populations, especially Tibetan individuals. This study aims to determine whether variations in these two genes correlate with gout-related indices in Chinese-Tibetan gout patients. Eleven single-nucleotide polymorphisms in the WDR1 and CLNK genes were detected in 319 Chinese-Tibetan gout patients and 318 controls. We used one-way analysis of variance to evaluate the polymorphisms' effects on gout based on mean serum levels of metabolism indicators, such as albumin, glucose (GLU), triglycerides, cholesterol, high-density lipoproteins (HDL-C), creatinine, and uric acid, from fasting venous blood samples. All p values were Bonferroni corrected. Polymorphisms of the WDR1 and CLNK genes affected multiple risk factors for gout development. Significant differences in serum GLU levels were detected between different genotypic groups with WDRI polymorphisms rs4604059 (p = 0.005) and rs12498927 (p = 0.005). In addition, significant differences in serum HDL-C levels were detected between different genotypic groups with the CLNK polymorphism rs2041215 (p = 0.001). Polymorphisms of CLNK also affected levels of albumin, triglycerides, and creatinine. This study is the first to investigate and identify positive correlations between WDR1 and CLNK gene polymorphisms in Chinese-Tibetan populations. Our findings provide significant evidence for the effect of genetic polymorphisms on gout-related factors in Chinese-Tibetan populations.

  16. Harnessing high density lipoproteins to block transforming growth factor beta and to inhibit the growth of liver tumor metastases.

    Directory of Open Access Journals (Sweden)

    José Medina-Echeverz

    Full Text Available Transforming growth factor β (TGF-β is a powerful promoter of cancer progression and a key target for antitumor therapy. As cancer cells exhibit active cholesterol metabolism, high density lipoproteins (HDLs appear as an attractive delivery system for anticancer TGFβ-inhibitory molecules. We constructed a plasmid encoding a potent TGF-β-blocking peptide (P144 linked to apolipoprotein A-I (ApoA-I through a flexible linker (pApoLinkerP144. The ApoLinkerP144 sequence was then incorporated into a hepatotropic adeno-associated vector (AAVApoLinkerP144. The aim was to induce hepatocytes to produce HDLs containing a modified ApoA-I capable of blocking TGF-β. We observed that transduction of the murine liver with pApoLinkerP144 led to the appearance of a fraction of circulating HDL containing the fusion protein. These HDLs were able to attenuate TGF-β signaling in the liver and to enhance IL-12 -mediated IFN-γ production. Treatment of liver metastasis of MC38 colorectal cancer with AAVApoLinkerP144 resulted in a significant reduction of tumor growth and enhanced expression of IFN-γ and GM-CSF in cancerous tissue. ApoLinkerP144 also delayed MC38 liver metastasis in Rag2-/-IL2rγ-/- immunodeficient mice. This effect was associated with downregulation of TGF-β target genes essential for metastatic niche conditioning. Finally, in a subset of ret transgenic mice, a model of aggressive spontaneous metastatic melanoma, AAVApoLinkerP144 delayed tumor growth in association with increased CD8+ T cell numbers in regional lymph nodes. In conclusion, modification of HDLs to transport TGF-β-blocking molecules is a novel and promising approach to inhibit the growth of liver metastases by immunological and non-immunological mechanisms.

  17. High density lipoprotein is an inappropriate substrate for hepatic lipase in postmenopausal women.

    Science.gov (United States)

    Zago, Valeria; Miksztowicz, Verónica; Cacciagiú, Leonardo; Basilio, Francisco; Berg, Gabriela; Schreier, Laura

    2012-12-24

    HDL antiatherogenic effects would not only depend on its concentration but also on its biological quality. Hepatic lipase (HL) action on HDL acts in one of the last steps of reverse cholesterol transport. Cardiovascular risk increases after menopause, however HDL does not decrease even when HL is increased. We evaluated HDL capacity as a substrate of HL in healthy postmenopausal women (PMW). We studied 20 PMW (51-60 y) and 20 premenopausal (PreMW) (26-40 y). In fasting serum, lipid-lipoprotein profile and HDL composition were assessed. Optimal assay conditions for HDL/HL ex vivo incubation were established. Increasing HDL-triglyceride concentrations (0.015 to 0.20 mmol/l) were incubated with post-heparin plasma obtained from a single healthy donor as a source of HL. Free fatty acids were measured and kinetic parameters calculated: K(m)(app), inverse to enzyme affinity, and V(max). HDL composition in PMW exhibits triglyceride enrichment (p<0.001). Kinetic analysis revealed higher K(m)(app) in PMW [130 (40-380) vs 45 (20-91) mmol/l, p<0.0001)] correlating directly with HDL-triglycerides (r=0.7, p=0.0001). Catalytic efficiency, V(max)/K(m)(app) was reduced when compared to controls (p=0.0001). Triglyceride-enriched HDL from PMW constitutes a poor substrate for HL suggesting that this particle may not exert efficiently its antiatherogenic function, regardless of plasma concentration. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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....

  3. 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

  4. 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.

  5. Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density Lipoprotein Nanoparticles.

    Science.gov (United States)

    Xiong, Fangyuan; Nirupama, Sabnis; Sirsi, Shashank R; Lacko, Andras; Hoyt, Kenneth

    2017-01-01

    The abnormal tumor vasculature and the resulting abnormal microenvironment are major barriers to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation of anticancer agents. Reconstituted high-density lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via their overexpressed scavenger receptor type B1 (SR-B1) receptor. The goal of this study is to investigate the potential of noninvasive US therapy to further improve delivery and tumor uptake of the payload from rHDL NPs, preloaded with an infrared dye (IR-780), aimed to establish a surrogate chemotherapeutic model with optical localization. Athymic nude mice were implanted orthotopically with one million breast cancer cells (MDA-MB-231/Luc). Three weeks later, animals were divided into seven groups with comparable mean tumor size: control, low, moderate, and high concentration of rHDL NPs alone groups, as well as these three levels of rHDL NPs plus US therapy groups ( N = 7 to 12 animals per group), where low, moderate and high denote 5, 10, and 50 µg of the IR-780 dye payload per rHDL NP injection, respectively. The US therapy system included a single element focused transducer connected in series with a function generator and power amplifier. A custom 3D printed cone with an acoustically transparent aperture and filled with degassed water allowed delivery of focused US energy to the tumor tissue. US exposure involved a pulsed sequence applied for a duration of 5 min. Each animal in the US therapy groups received a slow bolus co-injection of MB contrast agent and rHDL NPs. Animals were imaged using a whole-body optical system to quantify intratumoral rHDL NP accumulation at baseline and again at 1 min, 30 min, 24 h, and 48 h. At 48 h, all animals were euthanized and tumors were excised for ex vivo analysis. We investigated a noninvasive optical imaging

  6. 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.

  7. 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.

  8. High-Density Lipoprotein Cholosterol May Discriminate Mild and Severe Preeclampsia

    Directory of Open Access Journals (Sweden)

    Esra Can

    2011-08-01

    CONCLUSIONS: Blood HDL cholesterol levels measured at delivery were reduced in patients with preeclampsia, and patients with reduced levels of HDL cholesterol had a substantially higher probability of the disease severity in comparision to those with mild preeclampsia or those controls.

  9. MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wolfe, Adam R.; Bambhroliya, Arvind [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reddy, Jay P. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Debeb, Bisrat G. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Huo, Lei [Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Larson, Richard; Li, Li [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Ueno, Naoto T. [Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-06-01

    Purpose: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. Methods and Materials: MiR-33a expression was analyzed by reverse transcriptase–polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Results: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a–expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a–expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a–expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a–expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P

  10. MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer

    International Nuclear Information System (INIS)

    Wolfe, Adam R.; Bambhroliya, Arvind; Reddy, Jay P.; Debeb, Bisrat G.; Huo, Lei; Larson, Richard; Li, Li; Ueno, Naoto T.; Woodward, Wendy A.

    2016-01-01

    Purpose: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. Methods and Materials: MiR-33a expression was analyzed by reverse transcriptase–polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. Results: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a–expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a–expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a–expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a–expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P

  11. Metabolism of triglyceride-rich lipoproteins and transfer of lipids to high-density lipoproteins (HDL) in vegan and omnivore subjects.

    Science.gov (United States)

    Vinagre, J C; Vinagre, C G; Pozzi, F S; Slywitch, E; Maranhão, R C

    2013-01-01

    Vegan diet excludes all foodstuffs of animal origin and leads to cholesterol lowering and possibly reduction of cardiovascular disease risk. The aim was to investigate whether vegan diet improves the metabolic pathway of triglyceride-rich lipoproteins, consisting in lipoprotein lipolysis and removal from circulation of the resulting remnants and to verify whether the diet alters HDL metabolism by changing lipid transfers to this lipoprotein. 21 vegan and 29 omnivores eutrophic and normolipidemic subjects were intravenously injected triglyceride-rich emulsions labeled with (14)C-cholesterol oleate and (3)H-triolein: fractional clearance rates (FCR, in min(-1)) were calculated from samples collected during 60 min for radioactive counting. Lipid transfer to HDL was assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified in supernatant after chemical precipitation of non-HDL fractions and nanoemulsion. Serum LDL cholesterol was lower in vegans than in omnivores (2.1 ± 0.8, 2.7 ± 0.7 mmol/L, respectively, p vegans than in omnivores (0.016 ± 0.012, 0.003 ± 0.003, p vegans than in omnivores (2.7 ± 0.6, 3.5 ± 1.5%, p vegans, but the lipolysis process, estimated by triglyceride FCR was equal. Increased removal of atherogenic remnants and diminution of cholesteryl ester transfer may favor atherosclerosis prevention by vegan diet. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. 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.

  13. Association of apolipoprotein M with high-density lipoprotein kinetics in overweight-obese men

    DEFF Research Database (Denmark)

    Ooi, Esther M M; Watts, Gerald F; Chan, Dick C

    2009-01-01

    cholesterol and HDL cholesterol (ptriglyceride, NEFA, insulin, glucose, HOMA score or adiponectin concentrations. Plasma apoM was positively associated with both apoA-I and apoA-II concentrations (r=0.406, p...%). The kinetics of HDL apoA-I and apoA-II were measured using intravenous administration of D(3)-leucine, gas chromatography-mass spectrometry and multi-compartmental modeling. RESULTS: Plasma apoM was inversely associated with body mass index and positively associated with plasma total cholesterol, LDL...... apoM and triglycerides were significant, independent predictors of HDL apoA-I FCR (adjusted R(2)=16%, p

  14. 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

  15. Kinetics of incorporation/redistribution of photosensitizer hypericin to/from high-density lipoproteins

    Czech Academy of Sciences Publication Activity Database

    Joniova, J.; Buriánková, L.; Búzová, Diana; Miškovský, P.; Jančura, D.

    2014-01-01

    Roč. 475, 1-2 (2014), s. 578-584 ISSN 0378-5173 Institutional support: RVO:67179843 Keywords : aggregation * drug delivery * fluorescence * high- and low- density lipoproteins * Hypericin Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 3.650, year: 2014

  16. Hepatic lipase, genetically elevated high-density lipoprotein, and risk of ischemic cardiovascular disease

    DEFF Research Database (Denmark)

    Johannsen, Trine Holm; Kamstrup, Pia R; Andersen, Rolf V

    2008-01-01

    73M, N193S, S267F, L334F, T383M, and -480c>t influence levels of lipids, lipoproteins, and apolipoproteins and risk of ICD. DESIGN: For the cross-sectional study, we genotyped 9003 individuals from the Copenhagen City Heart Study; hereof were 8971 individuals included in the prospective study, 1747...

  17. 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

  18. Osbpl8 deficiency in mouse causes an elevation of high-density lipoproteins and gender-specific alterations of lipid metabolism.

    Directory of Open Access Journals (Sweden)

    Olivier Béaslas

    Full Text Available OSBP-related protein 8 (ORP8 encoded by Osbpl8 is an endoplasmic reticulum sterol sensor implicated in cellular lipid metabolism. We generated an Osbpl8(-/- (KO C57Bl/6 mouse strain. Wild-type and Osbpl8KO animals at the age of 13-weeks were fed for 5 weeks either chow or high-fat diet, and their plasma lipids/lipoproteins and hepatic lipids were analyzed. The chow-fed Osbpl8KO male mice showed a marked elevation of high-density lipoprotein (HDL cholesterol (+79% and phospholipids (+35%, while only minor increase of apolipoprotein A-I (apoA-I was detected. In chow-fed female KO mice a less prominent increase of HDL cholesterol (+27% was observed, while on western diet the HDL increment was prominent in both genders. The HDL increase was accompanied by an elevated level of HDL-associated apolipoprotein E in male, but not female KO animals. No differences between genotypes were observed in lecithin:cholesterol acyltransferase (LCAT or hepatic lipase (HL activity, or in the fractional catabolic rate of fluorescently labeled mouse HDL injected in chow-diet fed animals. The Osbpl8KO mice of both genders displayed reduced phospholipid transfer protein (PLTP activity, but only on chow diet. These findings are consistent with a model in which Osbpl8 deficiency results in altered biosynthesis of HDL. Consistent with this hypothesis, ORP8 depleted mouse hepatocytes secreted an increased amount of nascent HDL into the culture medium. In addition to the HDL phenotype, distinct gender-specific alterations in lipid metabolism were detected: Female KO animals on chow diet showed reduced lipoprotein lipase (LPL activity and increased plasma triglycerides, while the male KO mice displayed elevated plasma cholesterol biosynthetic markers cholestenol, desmosterol, and lathosterol. Moreover, modest gender-specific alterations in the hepatic expression of lipid homeostatic genes were observed. In conclusion, we report the first viable OsbplKO mouse model

  19. Suppression of Remodeling Behaviors with Arachidonic Acid Modification for Enhanced in vivo Antiatherogenic Efficacies of Lovastatin-loaded Discoidal Recombinant High Density Lipoprotein.

    Science.gov (United States)

    He, Hongliang; Zhang, Mengyuan; Liu, Lisha; Zhang, Shuangshuang; Liu, Jianping; Zhang, Wenli

    2015-10-01

    A series of in vitro evaluation in our previous studies had proved that arachidonic acid (AA) modification could suppress the remodeling behaviors of lovastatin-loaded discoidal reconstituted high density lipoprotein (LT-d-rHDL) by restraining the reactivity with lecithin cholesterol acyltransferase (LCAT) for reducing undesired drug leakage. This study focuses on the investigation of AA-modified LT-d-rHDL (AA-LT-d-rHDL) in atherosclerotic New Zealand White (NZW) rabbit models to explore whether AA modification could enhance drug targeting delivery and improve antiatherogenic efficacies in vivo. After pharmacokinetics of AA-LT-d-rHDL modified with different AA amount were investigated in atherosclerotic NZW rabbits, atherosclerotic lesions targeting property was assessed by ex vivo imaging of aortic tree and drug distribution. Furthermore, their antiatherogenic efficacies were elaborately evaluated and compared by typical biochemical indices. With AA modification amount augmenting, circulation time of AA-LT-d-rHDL was prolonged, and drug accumulation in the target locus was increased, eventually the significant appreciation in antiatherogenic efficacies were further supported by lower level of bad cholesterol, decreased atherosclerotic lesions areas and mean intima-media thickness (MIT), markedly attenuated matrix metalloproteinase-9 (MMP-9) protein expression and macrophage infiltration. This proof-of-concept study demonstrated that AA-LT-d-rHDL could enhance drug accumulation in atherosclerotic lesion and impede atherosclerosis progression more effectively.

  20. Heterogeneity of high-density lipoprotein particles and insulin output during oral glucose tolerance test in men with coronary artery disease.

    Science.gov (United States)

    Iwanejko, J; Kwaśniak, M; Wybrańska, I; Hartwich, J; Guevara, I; Zdzienicka, A; Kruszelnicka-Kwiatkowska, O; Piwowarska, W; Miszczuk-Jamska, B; Dembińska-Kieć, A

    1996-03-01

    We compared the high-density lipoprotein (HDL) composition and particle heterogeneity in 60 nonobese (normal body mass index, BMI) men suffering from coronary artery disease (CAD) with normolipemia and normoinsulinemia with lower and higher insulin output during the oral glucose tolerance test (silent hyperinsulinemia). The apolipoprotein apoAI, apoAII, and apoE levels were higher in the high insulin response (HI) group than in low insulin response (LI) group. The ratio of apoAI versus total protein and the ratio of apoAI versus total cholesterol were increased in HI compared with LI. The lipid components in HDL were higher in LI than in HI, while for HDL2 they were higher in HI. The fractioning of HDL by gradient gel electrophoresis revealed a different pattern of HDL particles in both groups. The larger particles, HDL2b and HDL2a (mean particle diameters 10.6 and 9.2 nm, respectively), occur more frequently in HI patients (up to 60%) than in LI patients, whereas the smaller particles, HDL3a and HDL3b (mean particle diameters 8.6 and 7.8 nm, respectively), predominate in LI patients. Our results demonstrate that even in the normoglycemic, normocholesterolemic CAD patients, a high insulin output observed during the oral glucose tolerance test may be connected with a different HDL particle pattern, which suggests changes in the reverse cholesterol transport.

  1. 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.

  2. The Application of a Modified d-ROMs Test for Measurement of Oxidative Stress and Oxidized High-Density Lipoprotein

    Directory of Open Access Journals (Sweden)

    Fumiaki Ito

    2017-02-01

    Full Text Available Reactive oxygen species (ROS are involved in the initiation and progression of atherosclerosis. ROS-derived hydroperoxides, as an indicator of ROS production, have been measured by using the diacron reactive oxygen metabolites (d-ROMs test, which requires iron-containing transferrin in the reaction mixture. In this study we developed a modified d-ROMs test, termed the Fe-ROMs test, where iron ions were exogenously added to the reaction mixture. This modification is expected to exclude the assay variation that comes from different blood iron levels in individuals. In addition, this Fe-ROMs test was helpful for determining the class of plasma lipoproteins that are hydroperoxidized. Low-density lipoprotein/very low-density lipoprotein (LDL/VLDL and high-density lipoprotein (HDL were purified by use of an LDL/VLDL purification kit and the dextran sulfate-Mg2+ precipitation method, respectively; their hydroperoxide contents were assessed by performing the Fe-ROMs test. The majority of the hydroperoxides were detected only in the HDL fraction, not in the LDL/VLDL. Further detailed analysis of HDLs by size-exclusion high-performance liquid chromatography revealed that the hydroperoxide-containing molecules were small-sized HDLs. Because HDL was shown to be the principal vehicle for the plasma hydroperoxides, this Fe-ROMs test is a beneficial method for the assessment of oxidized-HDL levels. Indeed, Fe-ROMs levels were strongly associated with the levels of oxidized HDL, which were determined by performing the malondialdehyde-modified HDL enzyme immunoassay. In conclusion, the Fe-ROMs test using plasma itself or the HDL fraction after dextran sulfate-Mg2+ precipitation is useful to assess the functionality of HDL, because the oxidation of HDL impairs its antiatherogenic capacity.

  3. Association between ABCG1 polymorphism rs1893590 and high-density lipoprotein (HDL) in an asymptomatic Brazilian population.

    Science.gov (United States)

    Zago, V H S; Scherrer, D Z; Parra, E S; Panzoldo, N B; Alexandre, F; Nakandakare, E R; Quintão, E C R; de Faria, E C

    2015-03-01

    ATP binding cassette transporter G1 (ABCG1) promotes lipidation of nascent high-density lipoprotein (HDL) particles, acting as an intracellular transporter. SNP rs1893590 (c.-204A > C) of ABCG1 gene has been previously studied and reported as functional over plasma HDL-C and lipoprotein lipase activity. This study aimed to investigate the relationships of SNP rs1893590 with plasma lipids and lipoproteins in a large Brazilian population. Were selected 654 asymptomatic and normolipidemic volunteers from both genders. Clinical and anthropometrical data were taken and blood samples were drawn after 12 h fasting. Plasma lipids and lipoproteins, as well as HDL particle size and volume were determined. Genomic DNA was isolated for SNP rs1893590 detection by TaqMan(®) OpenArray(®) Real-Time PCR Plataform (Applied Biosystems). Mann-Whitney U, Chi square and two-way ANOVA were the used statistical tests. No significant differences were found in the comparison analyses between the allele groups for all studied parameters. Conversely, significant interactions were observed between SNP and age over plasma HDL-C, were volunteers under 60 years with AA genotype had increased HDL-C (p = 0.048). Similar results were observed in the group with body mass index (BMI) m(2), where volunteers with AA genotype had higher HDL-C levels (p = 0.0034), plus an increased HDL particle size (p = 0.01). These findings indicate that SNP rs1893590 of ABCG1 has a significant impact over HDL-C under asymptomatic clinical conditions in an age and BMI dependent way.

  4. A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein

    DEFF Research Database (Denmark)

    Whorton, Matthew R; Bokoch, Michael P; Rasmussen, Søren Gøgsig Faarup

    2007-01-01

    G protein-coupled receptors (GPCRs) respond to a diverse array of ligands, mediating cellular responses to hormones and neurotransmitters, as well as the senses of smell and taste. The structures of the GPCR rhodopsin and several G proteins have been determined by x-ray crystallography, yet...... the organization of the signaling complex between GPCRs and G proteins is poorly understood. The observations that some GPCRs are obligate heterodimers, and that many GPCRs form both homo- and heterodimers, has led to speculation that GPCR dimers may be required for efficient activation of G proteins. However......, technical limitations have precluded a definitive analysis of G protein coupling to monomeric GPCRs in a biochemically defined and membrane-bound system. Here we demonstrate that a prototypical GPCR, the beta2-adrenergic receptor (beta2AR), can be incorporated into a reconstituted high-density lipoprotein...

  5. Phospholipid transfer from vesicles to high density lipoproteins, catalyzed by human plasma phospholipid transfer protein

    International Nuclear Information System (INIS)

    Sweeny, S.A.

    1985-01-01

    Human plasma phospholipid transfer protein (PLTP) catalyzes the mass transfer of phosphatidylcholine (PC). Partial purification of PLTP yielded proteins with apparent M/sub r/ = 59,000 and 40,000 by SDS-PAGE. PLTP activity was measured by transfer of [ 14 C]L-α-dipalmitoyl PC from egg-PC vesicles to HDL. Activity was enhanced at low pH (4.5) upon addition of β-mercaptoethanol while Ca +2 and Na + had no effect. E/sub act/ for facilitated PC transfer was 18.2 +/- 2 kcal/mol. The donor specificity of PLTP was examined using vesicles containing egg-PC plus cholesterol or sphingomyelin. The fluidity of the donor membrane (measured by fluorescence polarization of diphenylhexatriene) correlated strongly with a decrease in PLTP activity. Phosphatidic acid did not affect activity. Increase in vesicle size reduced activity. The acceptor specificity of PLTP was examined using chemically modified HDL. PLTP activity increased up to 1.7-fold with an initial increase in negative charge and then decreased upon extensive modification. A mechanism is proposed where PLTP binds to vesicls and enhances the diffusion of PC into the medium where it is adsorbed by HDL

  6. Niacin extended-release/simvastatin combination therapy produces larger favorable changes in high-density lipoprotein particles than atorvastatin monotherapy

    Directory of Open Access Journals (Sweden)

    Toth PP

    2012-01-01

    Full Text Available Peter P Toth1, Kamlesh M Thakker2, Ping Jiang2, Robert J Padley21University of Illinois College of Medicine, Peoria, and CGH Medical Center, Sterling, 2Abbott, Abbott Park, IL, USABackground: The purpose of this research was to compare the effects of niacin extended-release in combination with simvastatin (NER/S versus atorvastatin monotherapy on high-density lipoprotein (HDL particle number and size in patients with hyperlipidemia or dyslipidemia from the SUPREME study.Methods: This was a post hoc analysis of patients (n = 137 who completed the SUPREME study and who had lipid particle number and size measurements at both baseline and at week 12 by nuclear magnetic resonance spectroscopy. Following ≥4 weeks without lipid-modifying therapy (washout period, the patients received NER/S 1000/40 mg/day for 4 weeks followed by NER/S 2000/40 mg/day for 8 weeks, or atorvastatin 40 mg/day for 12 weeks. Median percent changes in HDL particle number and size from baseline to week 12 were compared between the NER/S and atorvastatin treatment groups using the Wilcoxon rank-sum test. Distribution of HDL particle subclasses at week 12 was compared between the treatment groups using the Cochran–Mantel–Haenszel test.Results: Treatment with NER/S resulted in a significantly greater percent reduction in small HDL particle number at week 12 compared with atorvastatin monotherapy (-1.8% versus 4.2%, P = 0.014, and a numerically greater percent increase in large HDL particle number (102.4% versus 39.2%, P = 0.078 compared with atorvastatin monotherapy. A significantly greater percent increase in HDL particle size from baseline at week 12 was observed with NER/S compared with atorvastatin (6.0% versus 1.3%, P < 0.001. NER/S treatment also resulted in a significant shift in HDL particle size from small and medium at baseline to large at week 12 (P < 0.0001.Conclusion: Treatment with NER/S resulted in larger favorable changes in number and size of HDL particle

  7. Prebeta-migrating high density lipoprotein: quantitation in normal and hyperlipidemic plasma by solid phase radioimmunoassay following electrophoretic transfer

    International Nuclear Information System (INIS)

    Ishida, B.Y.; Frolich, J.; Fielding, C.J.

    1987-01-01

    A quantitative solid phase immunoassay has been developed for the determination of the mass of electrophoretically separated prebeta apolipoprotein A-I (apoA-I) in human plasma. Conditions have been identified for the quantitative transfer and immunoblotting of the apolipoprotein in the absence of organic solvents or detergents. In normolipidemic plasma, the prebeta-migrating fraction of apoA-I represented 4.2 +/- 1.8% of total apoA-I (61 +/- 26 micrograms of apoA-I per ml of plasma). Significantly higher levels were found in hypercholesterolemia of genetic origin, in primary and secondary hypertriglyceridemia, and in congenital lecithin:cholesterol acyltransferase deficiency. In all cases prebeta-migrating apoA-I consisted in large part of low molecular weight lipoprotein species, compared to the size of the major, alpha-migrating apoA-I fraction

  8. Plasma levels of 27-hydroxycholesterol in humans and mice with monogenic disturbances of high density lipoprotein metabolism

    DEFF Research Database (Denmark)

    Karuna, Ratna; Holleboom, Adriaan G; Motazacker, Mohammad M

    2011-01-01

    Secretion of 27-hydroxycholesterol (27OHC) from macrophages is considered as an alternative to HDL-mediated reverse transport of excess cholesterol. We investigated 27OHC-concentrations in plasma of humans and mice with monogenic disorders of HDL metabolism. As compared to family controls mutations...... activities of LCAT and CETP, respectively, than the formation and transfer of cholesterylesters. 27OHC plasma levels were also decreased in apoA-I-, ABCA1- or LCAT-knockout mice but increased in SR-BI-knockout mice. Transplantation of ABCA1- and/or ABCG1-deficient bone marrow into LDL receptor deficient mice...... decreased plasma levels of 27OHC. In conclusion, mutations or absence of HDL genes lead to distinct alterations in the quantity, esterification or lipoprotein distribution of 27OHC. These findings argue against the earlier suggestion that 27OHC-metabolism in plasma occurs independently of HDL....

  9. 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

  10. Effect of serial infusions of reconstituted high-density lipoprotein (CER-001) on coronary atherosclerosis: rationale and design of the CARAT study.

    Science.gov (United States)

    Andrews, Jordan; Janssan, Alex; Nguyen, Tracy; Pisaniello, Anthony D; Scherer, Daniel J; Kastelein, John J P; Merkely, Bela; Nissen, Steven E; Ray, Kausik; Schwartz, Gregory G; Worthley, Stephen G; Keyserling, Connie; Dasseux, Jean-Louis; Butters, Julie; Girardi, Jacinta; Miller, Rosemary; Nicholls, Stephen J

    2017-02-01

    High-density lipoprotein (HDL) is believed to have atheroprotective properties, but an effective HDL-based therapy remains elusive. Early studies have suggested that infusion of reconstituted HDL promotes reverse cholesterol transport and vascular reactivity. The CER-001 Atherosclerosis Regression Acute Coronary Syndrome Trial (CARAT) is investigating the impact of infusing an engineered pre-beta HDL mimetic containing sphingomyelin (SM) and dipalmitoyl phosphatidlyglycerol (CER-001) on coronary atheroma volume in patients with a recent acute coronary syndrome (ACS). The CARAT is a phase 2, multicenter trial in which 292 patients with an ACS undergoing intracoronary ultrasonography and showing percent atheroma volume (PAV) greater than 30% are randomly assigned to treatment with ten infusions of CER-001 3 mg/kg or matching placebo, administered at weekly intervals. Intracoronary ultrasonography is repeated at the end of the treatment period. The primary endpoint is the nominal change in PAV. Safety and tolerability will also be evaluated. CARAT will establish whether serial 3 mg/kg infusions of an engineered pre-beta HDL mimetic containing SM and dipalmitoyl phosphatidlyglycerol (CER-001) will regress atherosclerotic plaque in patients with a recent ACS.

  11. 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...

  12. Raising high-density lipoprotein cholesterol for better prevention of cardiovascular disease

    NARCIS (Netherlands)

    Birjmohun, Rakesh S.; Stroes, Erik S. G.; Kastelein, John J. P.

    2007-01-01

    A substantial body of evidence supports the benefits of lipid lowering on cardiovascular outcome. As a consequence, statin therapy has emerged as the foundation for management of dyslipidemia in high-risk patients. Despite these achievements, two-thirds of cardiovascular events cannot be prevented

  13. Correlation between High Density Lipoprotein Cholesterol (HDL) Level and Aerobic Activity Level.

    Science.gov (United States)

    1987-04-01

    over a 40 day period for HDtJICholesteroll and Total Choleis- added with the "reverse" technique, This technique is only poai- tarot . The results are...Stand- tarot and Total Cholestero levels, it is beat that eet laoatr ard and a control Serum were each analyzed 10 times giving the * determinle its

  14. 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.

  15. 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.

  16. High density lipoprotein (HDL)-associated sphingosine 1-phosphate (S1P) inhibits macrophage apoptosis by stimulating STAT3 activity and survivin expression

    DEFF Research Database (Denmark)

    Feuerborn, Renata; Becker, Susen; Potì, Francesco

    2017-01-01

    BACKGROUND AND AIMS: Macrophage apoptosis is critically involved in atherosclerosis. We here examined the effect of anti-atherogenic high density lipoprotein (HDL) and its component sphingosine-1-phosphate (S1P) on apoptosis in RAW264.7 murine macrophages. METHODS: Mitochondrial or endoplasmic re...

  17. A one-step separation of human serum high density lipoproteins 2 and 3 by rate-zonal density gradient ultracentrifugation in a swinging bucket rotor

    NARCIS (Netherlands)

    Groot, P.H.E.; Scheek, L.M.; Havekes, L.; Noort, W.L. van; Hooft, F.M. van 't

    1982-01-01

    A method was developed for the separation of the high density lipoprotein subclasses HDL2 and HDL3 from human serum. Six serum samples are fractionated in a single-step ultracentrifugal procedure using the Beckman (SW-40) swinging bucket rotor. The method is based on a difference in flotation rate

  18. 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

  19. High-density lipoprotein-based therapy reduces the hemorrhagic complications associated with tissue plasminogen activator treatment in experimental stroke.

    Science.gov (United States)

    Lapergue, Bertrand; Dang, Bao Quoc; Desilles, Jean-Philippe; Ortiz-Munoz, Guadalupe; Delbosc, Sandrine; Loyau, Stéphane; Louedec, Liliane; Couraud, Pierre-Olivier; Mazighi, Mikael; Michel, Jean-Baptiste; Meilhac, Olivier; Amarenco, Pierre

    2013-03-01

    We have previously reported that intravenous injection of high-density lipoproteins (HDLs) was neuroprotective in an embolic stroke model. We hypothesized that HDL vasculoprotective actions on the blood-brain barrier (BBB) may decrease hemorrhagic transformation-associated with tissue plasminogen activator (tPA) administration in acute stroke. We used tPA alone or in combination with HDLs in vivo in 2 models of focal middle cerebral artery occlusion (MCAO) (embolic and 4-hour monofilament MCAO) and in vitro in a model of BBB. Sprague-Dawley rats were submitted to MCAO, n=12 per group. The rats were then randomly injected with tPA (10 mg/kg) or saline with or without human plasma purified-HDL (10 mg/kg). The therapeutic effects of HDL and BBB integrity were assessed blindly 24 hours later. The integrity of the BBB was also tested using an in vitro model of human cerebral endothelial cells under oxygen-glucose deprivation. tPA-treated groups had significantly higher mortality and rate of hemorrhagic transformation at 24 hours in both MCAO models. Cotreatment with HDL significantly reduced stroke-induced mortality versus tPA alone (by 42% in filament MCAO, P=0.009; by 73% in embolic MCAO, P=0.05) and tPA-induced intracerebral parenchymal hematoma (by 92% in filament MCAO, by 100% in embolic MCAO; Phemorrhagic transformation in rat models of MCAO. Both in vivo and in vitro results support the vasculoprotective action of HDLs on BBB under ischemic conditions.

  20. 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 ...

  1. Regression of coronary atherosclerosis with infusions of the high-density lipoprotein mimetic CER-001 in patients with more extensive plaque burden.

    Science.gov (United States)

    Kataoka, Yu; Andrews, Jordan; Duong, MyNgan; Nguyen, Tracy; Schwarz, Nisha; Fendler, Jessica; Puri, Rishi; Butters, Julie; Keyserling, Constance; Paolini, John F; Dasseux, Jean-Louis; Nicholls, Stephen J

    2017-06-01

    CER-001 is an engineered pre-beta high-density lipoprotein (HDL) mimetic, which rapidly mobilizes cholesterol. Infusion of CER-001 3 mg/kg exhibited a potentially favorable effect on plaque burden in the CHI-SQUARE (Can HDL Infusions Significantly Quicken Atherosclerosis Regression) study. Since baseline atheroma burden has been shown as a determinant for the efficacy of HDL infusions, the degree of baseline atheroma burden might influence the effect of CER-001. CHI-SQUARE compared the effect of 6 weekly infusions of CER-001 (3, 6 and 12 mg/kg) vs. placebo on coronary atherosclerosis in 369 patients with acute coronary syndrome (ACS) using serial intravascular ultrasound (IVUS). Baseline percent atheroma volume (B-PAV) cutoff associated with atheroma regression following CER-001 infusions was determined by receiver-operating characteristics curve analysis. 369 subjects were stratified according to the cutoff. The effect of CER-001 at different doses was compared to placebo in each group. A B-PAV ≥30% was the optimal cutoff associated with PAV regression following CER-001 infusions. CER-001 induced PAV regression in patients with B-PAV ≥30% but not in those with B-PAV CER-001 3mg/kg in patients with B-PAV ≥30% (-0.96%±0.34% vs. -0.25%±0.31%, P=0.01), whereas there were no differences between placebo (+0.09%±0.36%) versus CER-001 in patients with B-PAV CER-001 3 mg/kg induced the greatest atheroma regression in ACS patients with higher B-PAV. These findings identify ACS patients with more extensive disease as most likely to benefit from HDL mimetic therapy.

  2. 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.

  3. 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.

  4. 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.

  5. Apolipoprotein A-I configuration and cell cholesterol efflux activity of discoidal lipoproteins depend on the reconstitution process.

    Science.gov (United States)

    Cuellar, Luz Ángela; Prieto, Eduardo Daniel; Cabaleiro, Laura Virginia; Garda, Horacio Alberto

    2014-01-01

    Discoidal high-density lipoproteins (D-HDL) are critical intermediates in reverse cholesterol transport. Most of the present knowledge of D-HDL is based on studies with reconstituted lipoprotein complexes of apolipoprotein A-I (apoA-I) obtained by cholate dialysis (CD). D-HDL can also be generated by the direct microsolubilization (DM) of phospholipid vesicles at the gel/fluid phase transition temperature, a process mechanistically similar to the "in vivo" apoAI lipidation via ABCA1. We compared the apoA-I configuration in D-HDL reconstituted with dimyristoylphosphatidylcholine by both procedures using fluorescence resonance energy transfer measurements with apoA-I tryptophan mutants and fluorescently labeled cysteine mutants. Results indicate that apoA-I configuration in D-HDL depends on the reconstitution process and are consistent with a "double belt" molecular arrangement with different helix registry. As reported by others, a configuration with juxtaposition of helices 5 of each apoAI monomer (5/5 registry) predominates in D-HDL obtained by CD. However, a configuration with helix 5 of one monomer juxtaposed with helix 2 of the other (5/2 registry) would predominate in D-HDL generated by DM. Moreover, we also show that the kinetics of cholesterol efflux from macrophage cultures depends on the reconstitution process, suggesting that apoAI configuration is important for this HDL function. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Rational Targeting of Cellular Cholesterol in Diffuse Large B-Cell Lymphoma (DLBCL) Enabled by Functional Lipoprotein Nanoparticles: A Therapeutic Strategy Dependent on Cell of Origin.

    Science.gov (United States)

    Rink, Jonathan S; Yang, Shuo; Cen, Osman; Taxter, Tim; McMahon, Kaylin M; Misener, Sol; Behdad, Amir; Longnecker, Richard; Gordon, Leo I; Thaxton, C Shad

    2017-11-06

    Cancer cells have altered metabolism and, in some cases, an increased demand for cholesterol. It is important to identify novel, rational treatments based on biology, and cellular cholesterol metabolism as a potential target for cancer is an innovative approach. Toward this end, we focused on diffuse large B-cell lymphoma (DLBCL) as a model because there is differential cholesterol biosynthesis driven by B-cell receptor (BCR) signaling in germinal center (GC) versus activated B-cell (ABC) DLBCL. To specifically target cellular cholesterol homeostasis, we employed high-density lipoprotein-like nanoparticles (HDL NP) that can generally reduce cellular cholesterol by targeting and blocking cholesterol uptake through the high-affinity HDL receptor, scavenger receptor type B-1 (SCARB1). As we previously reported, GC DLBCL are exquisitely sensitive to HDL NP as monotherapy, while ABC DLBCL are less sensitive. Herein, we report that enhanced BCR signaling and resultant de novo cholesterol synthesis in ABC DLBCL drastically reduces the ability of HDL NPs to reduce cellular cholesterol and induce cell death. Therefore, we combined HDL NP with the BCR signaling inhibitor ibrutinib and the SYK inhibitor R406. By targeting both cellular cholesterol uptake and BCR-associated de novo cholesterol synthesis, we achieved cellular cholesterol reduction and induced apoptosis in otherwise resistant ABC DLBCL cell lines. These results in lymphoma demonstrate that reduction of cellular cholesterol is a powerful mechanism to induce apoptosis. Cells rich in cholesterol require HDL NP therapy to reduce uptake and molecularly targeted agents that inhibit upstream pathways that stimulate de novo cholesterol synthesis, thus, providing a new paradigm for rationally targeting cholesterol metabolism as therapy for cancer.

  7. 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

  8. 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...

  9. 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

  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. 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...

  12. 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.

  13. 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)

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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 ...

  19. 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...

  20. 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

  1. Cholesteryl ester transfer protein decreases high-density lipoprotein and severely aggravates atherosclerosis in APOE*3-Leiden mice

    NARCIS (Netherlands)

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

    2006-01-01

    OBJECTIVE - The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is still undergoing debate. Therefore, we evaluated the effect of human CETP expression on atherosclerosis in APOE*3-Leiden (E3L) mice with a humanized lipoprotein profile. METHODS AND RESULTS -

  2. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease: cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study

    DEFF Research Database (Denmark)

    Wittrup, HH; Andersen, RV; Tybjærg-Hansen, A

    2006-01-01

    CONTEXT: Genetic variants in lipoprotein lipase may affect triglycerides, high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD). OBJECTIVE: The objective of this study was to investigate the influence of T(-93)G, G(-53)C, Asp9Asn, Gly188Glu, Asn291Ser, and Ser447Ter lipoprotein...... lipase genotypes on triglycerides, HDL, and IHD. DESIGN: The cross-sectional study involved 9004 adults. The prospective study consisted of 8817 adults developing 1001 IHD events over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts of 915 and 1062 IHD patients, respectively....... SETTING: The study was performed in the Danish general population (the Copenhagen City Heart Study). PARTICIPANTS: IHD was angina pectoris or myocardial infarction. MAIN OUTCOME MEASURES: Triglycerides, HDL, and IHD were the main outcome measures. RESULTS: Cross-sectionally, triglycerides varied...

  3. 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 ...

  4. 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...

  5. 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)

  6. Effect of mono-unsaturated fatty acids versus complex carbohydrates on high-density lipoproteins in healthy men and women.

    NARCIS (Netherlands)

    Mensink, R.P.; Katan, M.B.

    1987-01-01

    The effects of two strictly controlled diets, one rich in complex carbohydrates, the other rich in olive oil, on serum lipids were studied in healthy men and women. Serum cholesterol levels fell on average by 0?44 mmol/l in the carbohydrate group and 0?46 mmol/l in the olive oil group. HDL

  7. Reversible flow of cholesteryl ester between high-density lipoproteins and triacylglycerol-rich particles is modulated by the fatty acid composition and concentration of triacylglycerols

    Directory of Open Access Journals (Sweden)

    E.C.R. Quintão

    2010-12-01

    Full Text Available We determined the influence of fasting (FAST and feeding (FED on cholesteryl ester (CE flow between high-density lipoproteins (HDL and plasma apoB-lipoprotein and triacylglycerol (TG-rich emulsions (EM prepared with TG-fatty acids (FAs. TG-FAs of varying chain lengths and degrees of unsaturation were tested in the presence of a plasma fraction at d > 1.21 g/mL as the source of CE transfer protein. The transfer of CE from HDL to FED was greater than to FAST TG-rich acceptor lipoproteins, 18% and 14%, respectively. However, percent CE transfer from HDL to apoB-containing lipoproteins was similar for FED and FAST HDL. The CE transfer from HDL to EM depended on the EM TG-FA chain length. Furthermore, the chain length of the monounsaturated TG-containing EM showed a significant positive correlation of the CE transfer from HDL to EM (r = 0.81, P < 0.0001 and a negative correlation from EM to HDL (r = -041, P = 0.0088. Regarding the degree of EM TG-FAs unsaturation, among EMs containing C18, the CE transfer was lower from HDL to C18:2 compared to C18:1 and C18:3, 17.7%, 20.7%, and 20%, respectively. However, the CE transfer from EMs to HDL was higher to C18:2 than to C18:1 and C18:3, 83.7%, 51.2%, and 46.3%, respectively. Thus, the EM FA composition was found to be the rate-limiting factor regulating the transfer of CE from HDL. Consequently, the net transfer of CE between HDL and TG-rich particles depends on the specific arrangement of the TG acyl chains in the lipoprotein particle core.

  8. The Ratio of Unesterified/esterified Cholesterol is the Major Determinant of Atherogenicity of Lipoprotein Fractions.

    Science.gov (United States)

    Bagheri, Babak; Alikhani, Asal; Mokhtari, Hossein; Rasouli, Mehdi

    2018-04-01

    The hypothesis is proposed that the atherogenicity of lipoporotein fractions is correlated with the content of unesterified cholesterol. To evaluate the role and prognostic values of unesterified and esterified cholesterol in lipoprotein fractions for coronary artery disease (CAD). The study population consisted of 400 patients who were divided to CAD controls and cases according to the data of coronary angiography. Fractional cholesterol esterification (FCE) as well as the complete profile of lipids and (apo)lipoproteins were determined. Total cholesterol was increased significantly in CAD patients (196.3 ± 52.3 mg/dL vs. 185.7 ± 48.0, p≤ 0.049) and the increment occurred totally in unesterified portion (77.2 ± 28.4 mg/dL vs. 71.1 ± 24.4, p≤ 0.031). HDL cholesterol showed a significant decrease in CAD group (39.9 ± 9.5 mg/dL vs. 44.6 ± 10.5, p≤ 0.001), but the decrement occurred wholly in the esterified portion (26.2 ± 9.2 mg/dL vs. 31.1 ± 8.1, p≤ 0.001). NonHDL cholesterol was increased significantly in CAD group (156.8 ± 48.3 mg/dL vs. 140.3 ± 43.6, p≤ 0.001), and the changes occurred in both un- and esterified portions. FCE in HDL was diminished significantly in CAD patients (64.8 ± 13.9% vs. 69.3 ± 7.9, p≤ 0.01). In multivariate logistic regression analysis, unesterified cholesterol in NonHDL (UeNonHDLc) and esterified cholesterol in HDL (EsHDLc) excluded total cholesterol and HDLc respectively from the regression equation. In ROC analysis, the ratio of UeNonHDLc/EsHDLc was the strongest predictor for CAD among cholesterol subfractions. The results confirm that UeNonHDLc is atherogenic and EsHDLc is antiatherogenic and are independent risk factors for CAD.

  9. 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.

  10. The effect of an apolipoprotein A-I-containing high-density lipoprotein-mimetic particle (CER-001) on carotid artery wall thickness in patients with homozygous familial hypercholesterolemia: The Modifying Orphan Disease Evaluation (MODE) study.

    Science.gov (United States)

    Hovingh, G Kees; Smits, Loek P; Stefanutti, Claudia; Soran, Handrean; Kwok, See; de Graaf, Jacqueline; Gaudet, Daniel; Keyserling, Constance H; Klepp, Heather; Frick, Jennifer; Paolini, John F; Dasseux, Jean-Louis; Kastelein, John J P; Stroes, Erik S

    2015-05-01

    Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH. Copyright © 2015 Mosby, Inc. All rights reserved.

  11. 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

  12. Interaction of estradiol and high density lipoproteins on proliferation of the human breast cancer cell line MCF-7 adapted to grow in serum free conditions

    International Nuclear Information System (INIS)

    Jozan, S.; Faye, J.C.; Tournier, J.F.; Tauber, J.P.; David, J.F.; Bayard, F.

    1985-01-01

    The responsiveness of the human mammary carcinoma cell line MCF-7 to estradiol and tamoxifen treatment has been studied in different culture conditions. Cells from exponentially growing cultures were compared with cells in their initial cycles after replating from confluent cultures (''confluent-log'' cells). It has been observed that estradiol stimulation of tritiated thymidine incorporation decreases with cell density and that ''confluent-log'' cells are estrogen unresponsive for a period of four cell cycles in serum-free medium conditions. On the other hand, growth of cells replated from exponentially growing, as well as from confluent cultures, can be inhibited by tamoxifen or a combined treatment with tamoxifen and the progestin levonorgestrel. This growth inhibitory effect can be rescued by estradiol when cells are replated from exponentially growing cultures. The growth inhibitory effect cannot be rescued by estradiol alone (10(-10) to 10(-8) M) when cells are replated from confluent cultures. In this condition, the addition of steroid depleted serum is necessary to reverse the state of estradiol unresponsiveness. Serum can be replaced by high density lipoproteins but not by low density lipoproteins or lipoprotein deficient serum. The present data show that estradiol and HDL interact in the control of MCF-7 cell proliferation

  13. Modified high-density lipoproteins by artificial sweetener, aspartame, and saccharin, showed loss of anti-atherosclerotic activity and toxicity in zebrafish.

    Science.gov (United States)

    Kim, Jae-Yong; Park, Ki-Hoon; Kim, Jihoe; Choi, Inho; Cho, Kyung-Hyun

    2015-01-01

    Safety concerns have been raised regarding the association of chronic consumption of artificial sweeteners (ASs) with metabolic disorders, especially in the heart and brain. There has been no information on the in vivo physiological effects of AS consumption in lipoprotein metabolism. High-dosage treatment (final 25, 50, and 100 mM) with AS (aspartame, acesulfame K, and saccharin) to human high-density lipoprotein (HDL) induced loss of antioxidant ability along with elevated atherogenic effects. Aspartame-treated HDL3 (final 100 mM) almost all disappeared due to putative proteolytic degradation. Aspartame- and saccharin-treated HDL3 showed more enhanced cholesteryl ester transfer activity, while their antioxidant ability was disappeared. Microinjection of the modified HDL3 exacerbated the inflammatory death in zebrafish embryos in the presence of oxLDL. These results show that AS treatment impaired the beneficial functions of HDL, resulting in loss of antioxidant and anti-atherogenic activities. These results suggest that aspartame and saccharin could be toxic to the human circulation system as well as embryonic development via impairment of lipoprotein function.

  14. 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

  15. 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

  16. 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.

  17. Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography

    Czech Academy of Sciences Publication Activity Database

    Dobiášová, Milada; Frohlich, J.; Šedová, Michaela; Cheung, M. C.; Brown, B.G.

    2011-01-01

    Roč. 52, č. 3 (2011), s. 566-571 ISSN 0022-2275 R&D Projects: GA MZd(CZ) NR8328; GA MŠk(CZ) 1M06014 Institutional research plan: CEZ:AV0Z50110509; CEZ:AV0Z10300504 Keywords : fractional esterification rate (FERHDL). * log(TG/HDL-Cholesterol) * AIP * biomarkers of cardiovascular risk * lipoprotein particle size * HDL- Atherosclerosis Treatment Study (HATS) Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 5.559, year: 2011

  18. 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

  19. 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

  20. 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....

  1. 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

  2. 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

  3. AMPK activation enhances the anti-atherogenic effects of high density lipoproteins in apoE-/- mice.

    Science.gov (United States)

    Ma, Ang; Wang, Jing; Yang, Liu; An, Yuanyuan; Zhu, Haibo

    2017-08-01

    HDL plays crucial roles at multiple stages of the pathogenesis of atherosclerosis. AMP-activated protein kinase (AMPK) is a therapeutic candidate for the treatment of cardiovascular disease. However, the effect of AMPK activation on HDL functionality has not been established in vivo. We assessed the effects of pharmacological AMPK activation using A-769662, AICAR, metformin, and IMM-H007 on the atheroprotective functions of HDL in apoE-deficient (apoE -/- ) mice fed with a high-fat diet. After administration, there were no changes in serum lipid levels among the groups. However, mice treated with AMPK activators showed significantly enhanced reverse cholesterol transport in vivo and in vitro. AMPK activation also increased the expression of ABCA1 and ABCG1 in macrophages and scavenger receptor class B type I and LCAT in the liver. HDL from AMPK activation mice exhibited lower HDL inflammatory index and myeloperoxidase activity and higher paraoxonase 1 activity than HDL from untreated mice, implying superior antioxidant and anti-inflammatory capacities. Pharmacological AMPK activation also induced polarization of macrophages to the M2 state and reduced plasma lipid peroxidation, inflammatory cytokine production, and atherosclerotic plaque formation in apoE -/- mice. These observations suggest that pharmacological AMPK activation enhances the anti-atherogenic properties of HDL in vivo. This likely represents a key mechanism by which AMPK activation attenuates atherosclerosis. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. 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.

  5. 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.

  6. 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

  7. 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

  8. Determinants of total and high density lipoprotein cholesterol in boys and men with special reference to diet

    NARCIS (Netherlands)

    Knuiman, J.T.

    1983-01-01

    At present it is assumed that atherosclerosis begins in childhood and that this process may ultimately result in the manifestations of coronary heart disease later in life. For this reason it is relevant to study the distribution of risk indicators for coronary heart disease (CHD) in children from

  9. EFEK PEMBERIAN SUSU SAPI BUBUK TERHADAP KADAR SERUM HDL (HIGH DENSITY LIPOPROTEIN PADA TIKUS PUTIH (Rattus norvegicus GALUR WISTAR MODEL DIABETES MELITUS TIPE 2

    Directory of Open Access Journals (Sweden)

    Zakia Umami

    2015-05-01

    Full Text Available ABSTRACTThe purpose of this study was to determine the cow’s milk powder to increased serum levels of High Density Lipoprotein (HDL of white male rat model with diabetes mellitus type 2. The design of this study was a post-test control group study conducted in 30 male rats which randomly divided into five groups. Negative control group was the group of rats which fed normally, the positive control group was induced by streptozotocin (STZ without given cow’s milk, group P1, P2, P3 were given a normal diet and cow’s milk 0.9; 1.8, and 2.7 g orally every day. The results of this study were the levels of HDL in K(-=44.22 mg/dl, K(+=47.45 mg/dl, P1=56.56 mg/dl, P2=51.82 mg/dl, and P3=59.45 mg/dl. The conclusion was the milk powder was not significantly increase levels of HDL (p>0.05. More longer intervention was suggested for further research to get more significant of HDL level on type 2 diabetes mellitus.Keywords: HDL serum level, high fat diet, milk powder, streptozotocinABSTRAKTujuan penelitian ini adalah menganalisis pengaruh pemberian susu sapi bubuk terhadap peningkatan kadar serum High Density Lipoprotein (HDL tikus putih (Rattus norvegicus berjenis kelamin jantan model diabetes melitus (DM tipe 2. Penelitian ini menggunakan desain penelitian post test control group dengan 30 ekor tikus dibagi secara acak menjadi lima kelompok. Kelompok K(- adalah tikus yang diberi pakan normal, kelompok K(+ diinduksi dengan streptozotocin (STZ tanpa diberi susu, kelompok P1 sampai P3 diberi diet normal dan susu 0,9; 1,8, dan 2,7 g secara oral setiap hari. Hasil penelitian menunjukkan kadar HDL pada K(-=44,22 mg/dl, K(+=47,45 mg/dl, P1=56,56 mg/dl, P2=51,82 mg/dl, dan P3=59,45 mg/dl. Susu sapi bubuk mampu meningkatkan kadar HDL tikus model DM tipe 2 akan tetapi tidak signifikan (p>0,05. Perlu dilakukan penelitian lebih lanjut dengan waktu lama penelitian yang berbeda sehingga bisa berdampak yang lebih signifikan untuk kadar HDL pada DM tipe 2.Kata kunci

  10. A prominent large high-density lipoprotein at birth enriched in apolipoprotein C-I identifies a new group of infancts of lower birth weight and younger gestational age

    Energy Technology Data Exchange (ETDEWEB)

    Kwiterovich Jr., Peter O.; Cockrill, Steven L.; Virgil, Donna G.; Garrett, Elizabeth; Otvos, James; Knight-Gibson, Carolyn; Alaupovic, Petar; Forte, Trudy; Farwig, Zachlyn N.; Macfarlane, Ronald D.

    2003-10-01

    Because low birth weight is associated with adverse cardiovascular risk and death in adults, lipoprotein heterogeneity at birth was studied. A prominent, large high-density lipoprotein (HDL) subclass enriched in apolipoprotein C-I (apoC-I) was found in 19 percent of infants, who had significantly lower birth weights and younger gestational ages and distinctly different lipoprotein profiles than infants with undetectable, possible or probable amounts of apoC-I-enriched HDL. An elevated amount of an apoC-I-enriched HDL identifies a new group of low birth weight infants.

  11. A diet rich in monounsaturated rapeseed oil reduces the lipoprotein cholesterol concentration and increases the relative content of n-3 fatty acids in serum in hyperlipidemic subjects.

    Science.gov (United States)

    Gustafsson, I B; Vessby, B; Ohrvall, M; Nydahl, M

    1994-03-01

    The effects of 3 wk on a diet rich in monounsaturated rapeseed oil were compared with those of a diet containing sunflower oil within a lipid-lowering diet. Ninety-five subjects with moderate hyperlipoproteinemia were randomly assigned to one of the two well-controlled diets prepared at the hospital kitchen. Total serum, low-density- and high-density-lipoprotein cholesterol concentrations decreased by 15%, 16%, and 11% (P oil diet and by 16%, 14%, and 13% (P oil diet. Serum triglycerides decreased more markedly (by 29%, P oil than on the rapeseed oil diet (14%, P oil diet but decreased on the sunflower oil diet. There was an increase in the alpha-tocopherol concentrations after both diets. The findings indicate that low erucic acid rapeseed oil can replace oils and fats rich in polyunsaturated fatty acids in a lipid-lowering diet.

  12. Novel function of lecithin-cholesterol acyltransferase. Hydrolysis of oxidized polar phospholipids generated during lipoprotein oxidation.

    Science.gov (United States)

    Goyal, J; Wang, K; Liu, M; Subbaiah, P V

    1997-06-27

    Although the major function of lecithin-cholesterol acyltransferase (LCAT) is cholesterol esterification, our previous studies showed that it can also hydrolyze platelet-activating factor (PAF). Because of the structural similarities between PAF and the truncated phosphatidylcholines (polar PCs) generated during lipoprotein oxidation, we investigated the possibility that LCAT may also hydrolyze polar PCs to lyso-PC during the oxidation of plasma. PAF acetylhydrolase (PAF-AH), which is known to hydrolyze polar PCs in human plasma, was completely inhibited by 0.2 mM p-aminoethyl benzenesulfonyl fluoride (Pefabloc), a new serine esterase inhibitor, which had no effect on LCAT at this concentration. On the other hand, 1 mM diisopropylfluorophosphate (DFP) completely inhibited LCAT but had no effect on PAF-AH. Polar PC accumulation during the oxidation of plasma increased by 44% in the presence of 0.2 mM Pefabloc and by 30% in the presence of 1 mM DFP. The formation of lyso-PC was concomitantly inhibited by both of the inhibitors. The combination of the two inhibitors resulted in the maximum accumulation of polar PCs, suggesting that both PAF-AH and LCAT are involved in their breakdown. Oxidation of chicken plasma, which has no PAF-AH activity, also resulted in the formation of lyso-PC from the hydrolysis of polar PC, which was inhibited by DFP. Polar PCs, either isolated from oxidized plasma or by oxidation of labeled synthetic PCs, were hydrolyzed by purified LCAT, which had no detectable PAF-AH activity. These results demonstrate a novel function for LCAT in the detoxification of polar PCs generated during lipoprotein oxidation, especially when the PAF-AH is absent or inactivated.

  13. High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro

    Science.gov (United States)

    Grün, Johanna L.; Manjarrez-Reyna, Aaron N.; Gómez-Arauz, Angélica Y.; Leon-Cabrera, Sonia; Bueno-Hernández, Nallely; Islas-Andrade, Sergio

    2018-01-01

    The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome. PMID:29850624

  14. High-Density Lipoproteins-Associated Proteins and Subspecies Related to Arterial Stiffness in Young Adults with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Xiaoting Zhu

    2018-01-01

    Full Text Available Lower plasma levels of high-density lipoproteins (HDL in adolescents with type 2 diabetes (T2D have been associated with a higher pulse wave velocity (PWV, a marker of arterial stiffness. Evidence suggests that HDL proteins or particle subspecies are altered in T2D and these may drive these relationships. In this work, we set out to reveal any specific proteins and subspecies that are related to arterial stiffness in youth with T2D from proteomics data. Plasma and PWV measurements were previously acquired from lean and T2D adolescents. Each plasma sample was separated into 18 fractions and evaluated by mass spectrometry. Then, we applied a validated network-based computational approach to reveal HDL subspecies associated with PWV. Among 68 detected phospholipid-associated proteins, we found that seven were negatively correlated with PWV, indicating that they may be atheroprotective. Conversely, nine proteins show positive correlation with PWV, suggesting that they may be related to arterial stiffness. Intriguingly, our results demonstrate that apoA-I and histidine-rich glycoprotein may reverse their protective roles and become antagonistic in the setting of T2D. Furthermore, we revealed two arterial stiffness-associated HDL subspecies, each of which contains multiple PWV-related proteins. Correlation and disease association analyses suggest that these HDL subspecies might link T2D to its cardiovascular-related complications.

  15. A Biomimic Reconstituted High-Density-Lipoprotein-Based Drug and p53 Gene Co-delivery System for Effective Antiangiogenesis Therapy of Bladder Cancer

    Science.gov (United States)

    Ouyang, Qiaohong; Duan, Zhongxiang; Jiao, Guangli; Lei, Jixiao

    2015-07-01

    A biomimic reconstituted high-density-lipoprotein-based drug and p53 gene co-delivery system (rHDL/CD-PEI/p53 complexes) was fabricated as a targeted co-delivery nanovector of drug and gene for potential bladder cancer therapy. Here, CD-PEI was utilized to effectively condense the p53 plasmid, to incorporate the plasmid into rHDL, and to act as an antitumor drug to suppress tumor angiogenesis. The rHDL/CD-PEI/p53 complexes exhibited desirable and homogenous particle size, neutral surface charge, and low cytotoxicity in vitro. The results of confocal laser scanning microscopy and flow cytometry confirmed that SR-BI-targeted function induced specific cytoplasmic delivery and high gene transfection efficiency in MBT-2 murine bladder cells. In addition, rHDL/CD-PEI/p53 complexes co-delivering CD and p53 gene achieved synergistic angiogenesis suppression by more effectively downregulating the expression of vascular endothelial growth factor (VEGF) messenger RNA (mRNA) and protein via different pathways in vitro. In vivo investigation on C3H/He mice bearing MBT-2 tumor xenografts revealed that rHDL/CD-PEI/p53 complexes possessed strong antitumor activity. These findings suggested that rHDL/CD-PEI/p53 complexes could be an ideal tumor-targeting system for simultaneous transfer of drug and gene, which might be a new promising strategy for effective bladder cancer therapy.

  16. High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro

    Directory of Open Access Journals (Sweden)

    Johanna L. Grün

    2018-01-01

    Full Text Available The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL- 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL and stimulated with lipopolysaccharide (LPS. The nonclassical monocyte (NCM percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome.

  17. Metabolism of apolipoproteins A-I and A-II in human high-density lipoprotein: a mathematical approach for analysis of their specific activity decay curves

    International Nuclear Information System (INIS)

    Atmeh, R.F.

    1987-01-01

    The differential rate equations describing the compartmental model of human high-density lipoprotein (HDL) were integrated by means of Laplace transforms and an exponential equation was obtained for each of the three compartments. These equations were used to fit the observed plasma decay data and give estimates for the rate constants of the system by means of a written computer program. Furthermore, these estimates were used to calculate the exponential constants of the integrated equations. Consequently, the amount of label in any of the intravascular, extravascular, and urine compartments can be calculated as a fraction of the original dose of label at any time point. This method was tested using data for the (AI)HDL subclass because it contains only apolipoprotein A-I as the major apolipoprotein and does not contain apolipoprotein A-II. The calculated plasma and urine radioactivity data were compared with the experimentally obtained data from two normolipoproteinemic subjects and found to be in good agreement. The significance of this method is its application to the analysis of the decay data of the individual apolipoproteins of (AI + AII) HDL subclass where the urinary radioactivity data resulting from the individual apolipoprotein breakdown on the native particle cannot be measured experimentally at present. Such data are essential for the detailed calculation of the kinetic parameters of these apolipoproteins

  18. High levels of Porphyromonas gingivalis-induced immunoglobulin G2 are associated with lower high-density lipoprotein levels in chronic periodontitis.

    Science.gov (United States)

    Ardila, Carlos M; Guzmán, Isabel C

    2016-11-01

    To investigate the association between the presence of Porphyromonas gingivalis-induced immunoglobulin G antibodies and the high-density lipoprotein (HDL) level. A total of 108 individuals were examined. The presence of P. gingivalis was detected using primers designed to target the 16S rRNA gene sequence. Peripheral blood was collected from each subject to determine the levels of P. gingivalis-induced IgG1 and IgG2 serum antibodies. The HDL levels were determined using fully enzymatic methods. A higher proportion of periodontitis patients had high levels of P. gingivalis-induced IgG1 and IgG2, and the proportion of subjects with a HDL level of chronic periodontitis patients. In the unadjusted regression model, the presence of high levels of P. gingivalis-induced IgG2 was associated with a HDL level of periodontitis patients with high levels of P. gingivalis-induced IgG2 showed 3.2 more chances of having pathological HDL levels (odds ratio = 3.2, 95% confidence interval = 1.2-9.8). High levels of P. gingivalis-induced IgG2 were associated with low HDL concentrations in patients with periodontitis, which suggests that the response of the host to periodontal infection may play an important role in the pathogenesis of cardiovascular diseases. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Effect of estrogen receptor-alpha (ESR1 gene polymorphism on high density lipoprotein levels in response to hormone replacement therapy

    Directory of Open Access Journals (Sweden)

    N.C. Nogueira-de-Souza

    2009-12-01

    Full Text Available Studies have shown that estrogen replacement therapy and estrogen plus progestin replacement therapy alter serum levels of total, LDL and HDL cholesterol levels. However, HDL cholesterol levels in women vary considerably in response to hormone replacement therapy (HRT. A significant portion of the variability of these levels has been attributed to genetic factors. Therefore, we investigated the influence of estrogen receptor-alpha (ESR1 gene polymorphisms on HDL levels in response to postmenopausal HRT. We performed a prospective cohort study on 54 postmenopausal women who had not used HRT before the study and had no significant general medical illness. HRT consisted of conjugated equine estrogen and medroxyprogesterone acetate continuously for 1 year. The lipoprotein levels were measured from blood samples taken before the start of therapy and after 1 year of HRT. ESR1 polymorphism (MspI C>T, HaeIII C>T, PvuII C>T, and XbaI A>G frequencies were assayed by restriction fragment length polymorphism. A general linear model was used to describe the relationships between HDL levels and genotypes after adjusting for age. A significant increase in HDL levels was observed after HRT (P = 0.029. Women with the ESR1 PvuII TT genotype showed a statistically significant increase in HDL levels after HRT (P = 0.032. No association was found between other ESR1 polymorphisms and HDL levels. According to our results, the ESR1 PvuII TT genotype was associated with increased levels of HDL after 1 year of HRT.

  20. 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

  1. 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

  2. A role for the high-density lipoprotein receptor SR-B1 in synovial inflammation via serum amyloid-A.

    LENUS (Irish Health Repository)

    Mullan, Ronan Hugh

    2012-02-01

    Acute phase apoprotein Serum Amyloid A (A-SAA), which is strongly expressed in rheumatoid arthritis synovial membrane (RA SM), induces angiogenesis, adhesion molecule expression, and matrix metalloproteinase production through the G-coupled receptor FPRL-1. Here we report alternative signaling through the high-density lipoprotein receptor scavenger receptor-class B type 1 (SR-B1). Quantitative expression\\/localization of SR-B1 in RA SM, RA fibroblast-like cells (FLCs), and microvascular endothelial cells (ECs) was assessed by Western blotting and immunohistology\\/fluorescence. A-SAA-mediated effects were examined using a specific antibody against SR-B1 or amphipathic alpha-Helical Peptides (the SR-B1 antagonists L-37pA and D-37pA), in RA FLCs and ECs. Adhesion molecule expression and cytokine production were quantified using flow cytometry and ELISA. SR-B1 was strongly expressed in the RA SM lining layer and endothelial\\/perivascular regions compared with osteoarthritis SM or normal control synovium. Differential SR-B1 expression in RA FLC lines (n = 5) and ECs correlated closely with A-SAA, but not tumor necrosis factor alpha-induced intercellular adhesion molecule-1 upregulation. A-SAA-induced interleukin-6 and -8 production was inhibited in the presence of anti-SR-B1 in human microvascular endothelial cells and RA FLCs. Moreover, D-37pA and L-37pA inhibited A-SAA-induced vascular cell adhesion molecule-1 and intercellular adhesion molecule expression from ECs in a dose-dependent manner. As SR-B1 is expressed in RA synovial tissue and mediates A-SAA-induced pro-inflammatory pathways, a better understanding of A-SAA-mediated inflammatory pathways may lead to novel treatment strategies for RA.

  3. The relationship between the high-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) and coronary in-stent restenosis.

    Science.gov (United States)

    Jing, Xiao-Dong; Wei, Xiao-Ming; Deng, Song-Bai; Du, Jian-Lin; Liu, Ya-Jie; She, Qiang

    2015-06-15

    High-density lipoprotein (HDL)-associated sphingosine-1-phosphate (S1P) contributed to several beneficial effects in the cardiovascular system. We explored the relationship between the HDL-S1P concentrations and coronary in-stent restenosis (ISR). Fifty consecutive patients with ISR and 50 normal control subjects were included. The serum S1P, HDL-S1P and clinical data were collected to explore the relationships between these parameters and ISR. The patients with ISR had significantly lower concentrations of serum S1P (96.10 ± 26.33 vs. 113.40 ± 32.72; P = 0.004) and HDL-S1P (32.81 ± 10.02 vs. 42.72 ± 11.75; P S1P: Quartile 1 (18.63-28.51 ng/ml), Quartile 2 (28.62-37.28 ng/ml), Quartile 3 (37.35-45.27 ng/ml), and Quartile 4 (45.59-79.36 ng/ml). The rates of ISR were 84%, 48%, 40% and 28%, respectively. The patients in Quartile 1 exhibited significantly higher rates of ISR compared with the other groups (P = 0.001). A multivariate stepwise logistic regression analysis indicated that HDL-S1P (OR = 0.846, 95% CI = 0.767-0.932, P = 0.001) was an independent predictor of ISR. An ROC analysis indicated that HDL-S1P = 30.37 ng/ml and had a 90% sensitivity and a 52% specificity in predicting ISR. HDL-S1P is an independent predictor of ISR, and patients with higher concentrations of HDL-S1P have a low risk of ISR. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. High density lipoprotein (HDL)-associated sphingosine 1-phosphate (S1P) inhibits macrophage apoptosis by stimulating STAT3 activity and survivin expression.

    Science.gov (United States)

    Feuerborn, Renata; Becker, Susen; Potì, Francesco; Nagel, Petra; Brodde, Martin; Schmidt, Harmut; Christoffersen, Christina; Ceglarek, Uta; Burkhardt, Ralph; Nofer, Jerzy-Roch

    2017-02-01

    Macrophage apoptosis is critically involved in atherosclerosis. We here examined the effect of anti-atherogenic high density lipoprotein (HDL) and its component sphingosine-1-phosphate (S1P) on apoptosis in RAW264.7 murine macrophages. Mitochondrial or endoplasmic reticulum-dependent apoptosis was induced by exposure of macrophages to etoposide or thapsigargin/fukoidan, respectively. Cell death induced by these compounds was inhibited by S1P as inferred from reduced annexin V binding, TUNEL staining, and caspase 3, 9 and 12 activities. S1P induced expression of the inhibitor of apoptosis protein (IAP) family proteins cIAP1, cIAP2 and survivin, but only the inhibitor of survivin expression YM155 and not the cIAP1/2 blocker GDC0152 reversed the inhibitory effect of S1P on apoptosis. Moreover, S1P activated signal transducer and activator of transcription 3 (STAT3) and Janus kinase 2 (JAK2) and the stimulatory effect of S1P on survivin expression and inhibitory effects on apoptosis were attenuated by STAT3 or JAK2 inhibitors, S3I-201 or AG490, respectively. The effects of S1P on STAT3 activation, survivin expression and macrophage apoptosis were emulated by HDL, HDL lipids, and apolipoprotein (apo) M-containing HDL, but not by apoA-I or HDL deprived of S1P or apoM. In addition, JTE013 and CAY10444, S1P receptor 2 and 3 antagonists, respectively, compromised the S1P and HDL capacities to stimulate STAT3 activation and survivin expression, and to inhibit apoptosis. HDL-associated S1P inhibits macrophage apoptosis by stimulating STAT3 activity and survivin expression. The suppression of macrophage apoptosis may represent a novel mechanism utilized by HDL to exert its anti-atherogenic effects. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Contributions of a disulfide bond and a reduced cysteine side chain to the intrinsic activity of the high-density lipoprotein receptor SR-BI.

    Science.gov (United States)

    Yu, Miao; Lau, Thomas Y; Carr, Steven A; Krieger, Monty

    2012-12-18

    The high-density lipoprotein (HDL) receptor scavenger receptor class B, type I (SR-BI), binds HDL and mediates selective cholesteryl ester uptake. SR-BI's structure and mechanism are poorly understood. We used mass spectrometry to assign the two disulfide bonds in SR-BI that connect cysteines within the conserved Cys(321)-Pro(322)-Cys(323) (CPC) motif and connect Cys(280) to Cys(334). We used site-specific mutagenesis to evaluate the contributions of the CPC motif and the side chain of extracellular Cys(384) to HDL binding and lipid uptake. The effects of CPC mutations on activity were context-dependent. Full wild-type (WT) activity required Pro(322) and Cys(323) only when Cys(321) was present. Reduced intrinsic activities were observed for CXC and CPX, but not XXC, XPX, or XXX mutants (X ≠ WT residue). Apparently, a free thiol side chain at position 321 that cannot form an intra-CPC disulfide bond with Cys(323) is deleterious, perhaps because of aberrant disulfide bond formation. Pro(322) may stabilize an otherwise strained CPC disulfide bond, thus supporting WT activity, but this disulfide bond is not absolutely required for normal activity. C(384)X (X = S, T, L, Y, G, or A) mutants exhibited altered activities that varied with the side chain's size: larger side chains phenocopied WT SR-BI treated with its thiosemicarbazone inhibitor BLT-1 (enhanced binding, weakened uptake); smaller side chains produced almost inverse effects (increased uptake:binding ratio). C(384)X mutants were BLT-1-resistant, supporting the proposal that Cys(384)'s thiol interacts with BLT-1. We discuss the implications of our findings on the functions of the extracellular loop cysteines in SR-BI and compare our results to those presented by other laboratories.

  6. Evaluation of the Combined Effect of Recombinant High-Density Lipoprotein Carrier and the Encapsulated Lovastatin in RAW264.7 Macrophage Cells Based on the Median-Effect Principle.

    Science.gov (United States)

    Jiang, Cuiping; Zhao, Yi; Yang, Yun; He, Jianhua; Zhang, Wenli; Liu, Jianping

    2018-03-05

    Recombinant high-density lipoprotein (rHDL) displays a similar anti-atherosclerotic effect with native HDL and could also be served as a carrier of cardiovascular drug for atherosclerotic plaque targeting. In our previous studies, rHDL has shown a more potent anti-atherosclerotic efficacy as compared to the other conventional nanoparticles with a payload of lovastatin (LS). Therefore, we hypothesized that a synergistic anti-atherosclerotic effect of the rHDL carrier and the encapsulated LS might exist. In this study, the dose-effect relationships and the combined effect of the rHDL and LS were quantitatively evaluated in RAW 264.7 macrophage cells using the median-effect analysis, in which the rHDL carrier was regarded as a drug combined. Median-effect analysis suggested that rHDL and LS exerted a desirable synergistic inhibition on the oxLDL internalization at a ratio of 6:1 ( D m,LS : D m,rHDL ) in RAW 264.7 macrophage cells. About 50% of the reduction on the intracellular lipid contents was found when RAW264.7 cells were treated with LS-loaded rHDLs at their respective median-effect dose ( D m ) concentrations and a synergistic effect on the mediating cholesterol efflux was also observed, which verified the accuracy of the results obtained from the median-effect analysis. The mechanism underlying the synergistic effect of the rHDL carrier and the drug might be attributed to their potent inhibitory effects on SR-A expression. In conclusion, the median-effect analysis was proven to be a feasible method to quantitatively evaluate the synergistic effect of the biofunctional carrier and the drug encapsulated.

  7. 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 ...

  8. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    International Nuclear Information System (INIS)

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-01-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

  9. 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" ...

  10. 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).

  11. High blood cholesterol levels

    Science.gov (United States)

    Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

  12. 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.

  13. 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...

  14. 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

  15. SCARB1 Gene Variants Are Associated With the Phenotype of Combined High High-Density Lipoprotein Cholesterol and High Lipoprotein (a)

    DEFF Research Database (Denmark)

    Yang, Xiaoping; Sethi, Amar A; Yanek, Lisa R

    2016-01-01

    variants in 6. Functional studies with 4 of the SCARB1 variants (c.386C>T, c.631-14T>G, c.4G>A, and c.631-53(m)C>T & c.726+55(m)CG>CA) showed decreased receptor function in vitro. CONCLUSIONS: Human SCARB1 gene variants are associated with a new lipid phenotype, characterized by high levels of both HDL...

  16. 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...

  17. Effect of 6 dietary fatty acids on the postprandial lipid profile, plasma fatty acids, lipoprotein lipase, and cholesterol ester transfer activities in healthy young men

    DEFF Research Database (Denmark)

    Tholstrup, T.; Sandstrøm, B.; Bysted, Anette

    2001-01-01

    , plasma fatty acids, and preheparin lipoprotein lipase and cholesterol ester transfer protein (CETP) activities. Design: Six test fats high (approximate to 43% by wt) in stearic acid, palmitic acid, palmitic + myristic acid, oleic acid, elaidic acid (trans 18:1), and linoleic acid were produced...... to the test-fat meals were observed for plasma lipoprotein triacylglycerol and cholesterol concentrations, plasma fatty acid concentrations, and lipoprotein lipase and CETP activities (diet x time interaction: 0.001 acids stearic and palmitic acids resulted......Background: There is increasing evidence that postprandial triacylglycerol-rich lipoproteins may be related to atherogenic risk. Objective: The objective was to investigate the effect of individual fatty acid intakes on postprandial plasma lipoprotein triacylglycerol and cholesterol concentrations...

  18. 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

  19. 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

  20. Effects of the high-density lipoprotein mimetic agent CER-001 on coronary atherosclerosis in patients with acute coronary syndromes: a randomized trial.

    Science.gov (United States)

    Tardif, Jean-Claude; Ballantyne, Christie M; Barter, Philip; Dasseux, Jean-Louis; Fayad, Zahi A; Guertin, Marie-Claude; Kastelein, John J P; Keyserling, Constance; Klepp, Heather; Koenig, Wolfgang; L'Allier, Philippe L; Lespérance, Jacques; Lüscher, Thomas F; Paolini, John F; Tawakol, Ahmed; Waters, David D

    2014-12-07

    High-density lipoproteins (HDLs) have several potentially protective vascular effects. Most clinical studies of therapies targeting HDL have failed to show benefits vs. placebo. To investigate the effects of an HDL-mimetic agent on atherosclerosis by intravascular ultrasonography (IVUS) and quantitative coronary angiography (QCA). A prospective, double-blinded, randomized trial was conducted at 51 centres in the USA, the Netherlands, Canada, and France. Intravascular ultrasonography and QCA were performed to assess coronary atherosclerosis at baseline and 3 (2-5) weeks after the last study infusion. Five hundred and seven patients were randomized; 417 and 461 had paired IVUS and QCA measurements, respectively. Patients were randomized to receive 6 weekly infusions of placebo, 3 mg/kg, 6 mg/kg, or 12 mg/kg CER-001. The primary efficacy parameter was the nominal change in the total atheroma volume. Nominal changes in per cent atheroma volume on IVUS and coronary scores on QCA were also pre-specified endpoints. The nominal change in the total atheroma volume (adjusted means) was -2.71, -3.13, -1.50, and -3.05 mm(3) with placebo, CER-001 3 mg/kg, 6 mg/kg, and 12 mg/kg, respectively (primary analysis of 12 mg/kg vs. placebo: P = 0.81). There was also no difference among groups for the nominal change in per cent atheroma volume (0.02, -0.02, 0.01, and 0.19%; nominal P = 0.53 for 12 mg/kg vs. placebo). Change in the coronary artery score was -0.022, -0.036, -0.022, and -0.015 mm (nominal P = 0.25, 0.99, 0.55), and change in the cumulative coronary stenosis score was -0.51, 2.65, 0.71, and -0.77% (compared with placebo, nominal P = 0.85 for 12 mg/kg and nominal P = 0.01 for 3 mg/kg). The number of patients with major cardiovascular events was 10 (8.3%), 16 (13.3%), 17 (13.7%), and 12 (9.8%) in the four groups. CER-001 infusions did not reduce coronary atherosclerosis on IVUS and QCA when compared with placebo. Whether CER-001 administered in other regimens or to other

  1. 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

  2. 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.

  3. 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.

  4. Cholesterol lipoproteins and prevalence of dyslipidemias in urban Asian Indians: A cross sectional study

    Directory of Open Access Journals (Sweden)

    Soneil Guptha

    2014-05-01

    Conclusions: Mean cholesterol and LDL cholesterol are low and triglycerides were high in urban Asian Indians. Most prevalent dyslipidemias are borderline high LDL, low HDL and high triglycerides. Subjects with high socioeconomic status, high fat intake and greater adiposity have higher total and LDL cholesterol and triglyceride and lower HDL cholesterol.

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. Effect of vitamin E supplementation on serumic levels of lipids and lipoproteins in cholesterol-fed male rat

    Directory of Open Access Journals (Sweden)

    M.H Khayat Nouri

    2008-11-01

    Full Text Available Hypercholesterolemia is one of the risk factors of cardiovascular diseases. High blood cholesterol affects the general health and increases the mortality rate of cardiovascular diseases. High levels of cholesterol in the diet increases LDL levels and decreases the activity of LDL receptors in the liver. Oxidation of vascular LDL lipoproteins increases the development of atherosclerosis. Previous studies have indicated that consumption of antioxidants decreases hypercholesterolemia. This study evaluates the effect of vitamin E supplementation on blood lipid levels in high cholesterol-fed rats. In this experimental study, three groups of male rats (n=10 for each group were used. The control group received basic diet and one of the other two groups received a diet containing one percent cholesterol and while the other received the same diet plus vitamin E supplement (2500 IU/kg in dry matter of the diet for one month. After determining the values of TC, LDL, VLDL, HDL and TG the results indicated that in rats fed with 1% cholesterol apart from HDL and VLDL the other lipids had increased significantly compared with the control group (p

  10. 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

  11. 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...

  12. 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.

  13. Chlordecone, a mixed pregnane X receptor (PXR) and estrogen receptor alpha (ERα) agonist, alters cholesterol homeostasis and lipoprotein metabolism in C57BL/6 mice

    International Nuclear Information System (INIS)

    Lee, Junga; Scheri, Richard C.; Zhang Yuan; Curtis, Lawrence R.

    2008-01-01

    Chlordecone (CD) is one of many banned organochlorine (OC) insecticides that are widespread persistent organic pollutants. OC insecticides alter lipid homeostasis in rodents at doses that are not neurotoxic or carcinogenic. Pretreatment of mice or rats with CD altered tissue distribution of a subsequent dose of [ 14 C]CD or [ 14 C]cholesterol (CH). Nuclear receptors regulate expression of genes important in the homeostasis of CH and other lipids. In this study, we report that CD suppresses in vitro reporter systems for human liver X receptors (LXRs) and activates those for human farnesoid X receptor (FXR), pregnane X receptor (PXR) and estrogen receptor α (ERα) in a concentration-dependent manner (0-50 μM). Consistent with human PXR activation in vitro, three days after a single dose of CD (15 mg/kg) hepatic microsomal CYP3A11 protein increases in C57BL/6 mice. CD decreases hepatic CH ester content without altering total CH concentration. Apolipoprotein A-I (apoA-I) contents of hepatic lipoprotein-rich and microsomal fractions of CD-treated mice are higher than controls. There is a significant reduction in non-high density lipoprotein CH but not apolipoprotein B-48/100 (apoB-48/100) in plasma from CD-treated mice after a 4 h fast. At 14 days after 15 mg CD/kg apoA-I and apoB-100 proteins but not CYP3A11 protein in hepatic microsomes are similar to controls. This work indicates that altered CH homeostasis is a mode of OC insecticide action of relevance after a single dose. This at least partially explains altered CH tissue distribution in CD-pretreated mice

  14. 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.

  15. Remnant lipoproteins

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G.

    2017-01-01

    Purpose of review: To review recent advances in the field of remnant lipoproteins and remnant cholesterol with a focus on cardiovascular disease risk. Recent findings: In line with previous years' research, current observational, genetic, and mechanistic studies find remnant lipoproteins (defined...... of cardiovascular disease risk reduction through remnant lipoprotein lowering are under way....

  16. Effect of Synthetic Truncated Apolipoprotein C-I Peptide on Plasma Lipoprotein Cholesterol in Nonhuman Primates

    Directory of Open Access Journals (Sweden)

    Rampratap S. Kushwaha

    2004-01-01

    Full Text Available The present studies were conducted to determine whether a synthetic truncated apoC-I peptide that inhibits CETP activity in baboons would raise plasma HDL cholesterol levels in nonhuman primates with low HDL levels. We used 2 cynomolgus monkeys and 3 baboons fed a cholesterol- and fat-enriched diet. In cynomolgus monkeys, we injected synthetic truncated apoC-I inhibitor peptide at a dose of 20 mg/kg and, in baboons, at doses of 10, 15, and 20 mg/kg at weekly intervals. Blood samples were collected 3 times a week and VLDL + LDL and HDL cholesterol concentrations were measured. In cynomolgus monkeys, administration of the inhibitor peptide caused a rapid decrease in VLDL + LDL cholesterol concentrations (30%–60% and an increase in HDL cholesterol concentrations (10%–20%. VLDL + LDL cholesterol concentrations returned to baseline levels in approximately 15 days. In baboons, administration of the synthetic inhibitor peptide caused a decrease in VLDL + LDL cholesterol (20%–60% and an increase in HDL cholesterol (10%–20%. VLDL + LDL cholesterol returned to baseline levels by day 21, whereas HDL cholesterol concentrations remained elevated for up to 26 days. ApoA-I concentrations increased, whereas apoE and triglyceride concentrations decreased. Subcutaneous and intravenous administrations of the inhibitor peptide had similar effects on LDL and HDL cholesterol concentrations. There was no change in body weight, food consumption, or plasma IgG levels of any baboon during the study. These studies suggest that the truncated apoC-I peptide can be used to raise HDL in humans.

  17. 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...

  18. marital status and occupation versus serum total cholesterol and hdl

    African Journals Online (AJOL)

    DR. AMIN

    ABSTRACT. The influence of marital status and occupation on serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL – CH) concentrations was studied in sixty one (61) adult male and female Hausa subjects aged 20 – 50 years. Irrespective of marital status and occupation, female subjects had higher ...

  19. 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

  20. [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.

  1. 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

  2. EFFECT OF THE LEVEL AND TYPE OF DIETARY FAT ON THE METABOLISM OF CHOLESTEROL AND BETA LIPOPROTEINS IN THE CEBUS MONKEY

    Science.gov (United States)

    Portman, Oscar W.; Hegsted, D. Mark; Stare, Fredrick J.; Bruno, Dorothy; Murphy, Robert; Sinisterra, Leonardo

    1956-01-01

    A study was carried out to determine the effect of the level and type of dietary fat on the concentration of cholesterol and beta lipoproteins in the sera of Cebus monkeys. Three groups of monkeys were fed isocaloric diets containing a fixed ratio of alpha protein and cholesterol to calories but with different amounts of corn oil and sucrose. Corn oil provided 10, 32, and 45 per cent of the calories in the three diets, and the level of sucrose was varied inversely. After 8 weeks the serum cholesterol and Sf 12 to 100 beta lipoprotein concentrations were significantly greater in the medium and high fat groups. When corn oil was decreased from 45 to 10 per cent of dietary calories and sucrose was increased, the serum cholesterol fell in all cases, and when the reverse change was made, the concentration of serum cholesterol increased. Variation in dietary sucrose had no specific effect. Substitution of starch for sucrose with diets otherwise constant did not cause significant change in the concentration of serum cholesterol. When monkeys fed corn oil diets at any of three levels were changed to hydrogenated cottonseed oil diets at the same level, the serum cholesterol and Sf 12 to 100 beta lipoproteins rose. However, hydrogenated cottonseed oil had no greater hypercholesteremic effect than did corn oil in the absence of dietary cholesterol. Diets containing lard with cholesterol also produced strikingly greater serum lipide responses than did diets based on corn oil and cholesterol. Hydrogenated cottonseed oil had a greater hypercholesteremic effect than an unhydrogenated cottonseed oil from the same lot. Preliminary studies indicated that the saturated fats (hydrogenated cottonseed oil) produced the most striking elevation of serum cholesterol values (above controls fed corn oil) when casein was the dietary protein. PMID:13376806

  3. 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 ...

  4. Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate

    Czech Academy of Sciences Publication Activity Database

    Dobiášová, Milada; Urbanová, Z.; Šamánek, M.

    2005-01-01

    Roč. 54, č. 2 (2005), s. 159-165 ISSN 0862-8408 R&D Projects: GA MZd(CZ) NA6590; GA MZd(CZ) NR8328 Institutional research plan: CEZ:AV0Z5011922 Keywords : particle size of lipoproteins * FER(HDL) * Log(TG/HDL-C) Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 1.806, year: 2005

  5. 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.

  6. [High-density lipoproteins (HDL) size and composition are modified in the rat by a diet supplemented with "Hass" avocado (Persea americana Miller)].

    Science.gov (United States)

    Pérez Méndez, Oscar; García Hernández, Lizbeth

    2007-01-01

    To determine the effects of dietary avocado on HDL structure and their associated enzyme, paraoxonase 1 (PON1). Fifteen Wistar male rats received avocado as part of their daily meal (5 g by 17.5 g chow diet), keeping the caloric intake similar to the control group (n=15) that received their usual chow diet. After 5 weeks, HDL were isolated by sequential ultracentrifugation and their size and chemical composition were analyzed. PON1 was determined in serum spectrophotometrically using phenylacetate as substrate. Rats that received avocado had about 27% lower triglycerides plasma levels whereas their HDL-cholesterol was 17% higher as compared to control group. The mean HDL Stokes diameter was significantly lower in avocado group (11.71 +/- 0.8 vs. 12.27 +/- 0.26 nm, in control group, p avocado group. HDL structural modifications induced by avocado were not related to modifications of LCAT and PLTP activities, but occurred in parallel with higher serum levels of PON1 activity when compared to the controls (57.4 +/- 8.9 vs. 43.0 +/- 5.6 micromol/min/mL serum, p avocado in the diet decreased plasma triglycerides, increased HDL-cholesterol plasma levels and modified HDL structure. The latter effect may enhance the antiatherogenic properties of HDL since PON1 activity also increased as a consequence of avocado.

  7. 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...

  8. 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...

  9. 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.

  10. Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

    NARCIS (Netherlands)

    J.A. Beentjes; A. van Tol (Arie); W.J. Sluiter (Wim); R.P.F. Dullaart (Robin)

    2000-01-01

    textabstractThe effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are

  11. 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

  12. 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

  13. Hematopoietic stem/progenitor cell proliferation and differentiation is differentially regulated by high-density and low-density lipoproteins in mice.

    Directory of Open Access Journals (Sweden)

    Yingmei Feng

    Full Text Available RATIONALE: Hematopoietic stem/progenitor cells (HSPC are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may increase HSPC proliferation and differentiation. OBJECTIVES: We hypothesized that LDL may enhance HSPC proliferation and differentiation while HDL might have the opposing effect which might influence the size of the pool of inflammatory cells. METHODS AND RESULTS: HSPC number and function were studied in hypercholesterolemic LDL receptor knockout (LDLr(-/- mice on high fat diet. Hypercholesterolemia was associated with increased frequency of HSPC, monocytes and granulocytes in the peripheral blood (PB. In addition, an increased proportion of BM HSPC was in G(2M of the cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors (GMP increased in BM of LDLr(-/- mice. When BM Lin-Sca-1+cKit+ (i.e. "LSK" cells were cultured in the presence of LDL in vitro we also found enhanced differentiation towards monocytes and granulocytes. Furthermore, LDL promoted lineage negative (Lin- cells motility. The modulation by LDL on HSPC differentiation into granulocytes and motility was inhibited by inhibiting ERK phosphorylation. By contrast, when mice were infused with human apoA-I (the major apolipoprotein of HDL or reconstituted HDL (rHDL, the frequency and proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL-induced monocyte and granulocyte differentiation in vitro. CONCLUSION: Our data suggest that LDL and HDL have opposing effects on HSPC proliferation and differentiation. It will be of interest to determine if breakdown of HSPC homeostasis by hypercholesterolemia contributes to inflammation and atherosclerosis progression.

  14. 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.

  15. [Effect of raw and cooked nopal (Opuntia ficus indica) ingestion on growth and profile of total cholesterol, lipoproteins, and blood glucose in rats].

    Science.gov (United States)

    Cárdenas Medellín, M L; Serna Saldívar, S O; Velazco de la Garza, J

    1998-12-01

    Two different concentrations (approx. 6 and 12%) and two presentations (raw and cooked) of dehydrated nopal were fed to laboratory rats and growth and serum total cholesterol, lipoprotein profile and glucose determined. Samples of raw and cooked nopal were chemically characterized for moisture, protein, ash, crude fiber, ether extract, total dietary fiber, reducing sugars, amino acids, minerals and gross energy. Cooking slightly affected some of the nutrients analyzed. After one month feeding, blood was withdrawn via intracardiac puncture and serum glucose, total cholesterol, HDL, LDL, and VLDL were determined. Rats fed 12% nopal had lower weight gains (P nopal or the control diet. Consumption of nopal did not affect (P > 0.05) glucose, total cholesterol and HDL cholesterol levels. However, rats fed raw nopal at the 12% concentration level had a 34% reduction in LDL cholesterol levels; thus, it was concluded that raw nopal had a potentially beneficial effect for hypercholesterolemic individuals.

  16. 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.

  17. Evidence for genetic factors explaining the association between birth weight and low-density lipoprotein cholesterol and possible intrauterine factors influencing the association between birth weight and high-density lipoprotein cholesterol: Analysis in twins

    NARCIS (Netherlands)

    IJzerman, R.G.; Stehouwer, C.D.A.; van Weissenbruch, M.M.; de Geus, E.J.C.; Boomsma, D.I.

    2001-01-01

    Recent studies have demonstrated an association between low weight at birth and an atherogenic lipid profile in later life. To examine the influences of intrauterine and genetic factors, we investigated 53 dizygotic and 61 monozygotic adolescent twin pairs. Regression analysis demonstrated that low

  18. Correction to: Dapagliflozin decreases small dense low-density lipoprotein-cholesterol and increases high-density lipoprotein 2-cholesterol in patients with type 2 diabetes: comparison with sitagliptin.

    Science.gov (United States)

    Hayashi, Toshiyuki; Fukui, Tomoyasu; Nakanishi, Noriko; Yamamoto, Saki; Tomoyasu, Masako; Osamura, Anna; Ohara, Makoto; Yamamoto, Takeshi; Ito, Yasuki; Hirano, Tsutomu

    2017-11-13

    Following publication of the original article [1], the authors identified a number of errors. In Result (P.3), Table 1 (P.4), Table 5 (P.9) and Supplementary Table 1, the correct unit for adiponectin was μg/mL. In Table 1 (P.4), the correct value for the post treatment body weight in dapagliflozin was 76.2±14.8. In Table 6 (P.10), the correct value for the pre treatment sd LDL/LDL-C in decreased LDL-C group was 0.38±0.10.

  19. Mechanism of action of gemfibrozil on lipoprotein metabolism.

    OpenAIRE

    Saku, K; Gartside, P S; Hynd, B A; Kashyap, M L

    1985-01-01

    Gemfibrozil is a potent lipid regulating drug whose major effects are to increase plasma high density lipoproteins (HDL) and to decrease plasma triglycerides (TG) in a wide variety of primary and secondary dyslipoproteinemias. Its mechanism of action is not clear. Six patients with primary familial endogenous hypertriglyceridemia with fasting chylomicronemia (type V lipoprotein phenotype) with concurrent subnormal HDL cholesterol levels (HDL deficiency) were treated initially by diet and once...

  20. 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 ...

  1. Plasma-Serum Cholesterol Differences in Children and Use of Measurements from Different Specimens

    NARCIS (Netherlands)

    Berentzen, N.E.; Wijga, A.H.; Rossem, van L.; Jongste, de J.C.; Boshuizen, H.C.; Smit, H.A.

    2013-01-01

    Background: We aimed to assess absolute plasma-serum differences and differences in ranking of total cholesterol (TC), high-density lipoprotein cholesterol (HDLC), and TC/HDLC ratio in children. Methods: We analysed data of 412 children participating in a Dutch birth cohort. TC, HDLC, and TC/HDLC

  2. 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.

  3. [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.

  4. Hepatic S1P deficiency lowers plasma cholesterol levels in apoB-containing lipoproteins when LDLR function is compromised.

    Science.gov (United States)

    Basu, Debapriya; Huq, Afroza; Iqbal, Jahangir; Hussain, M Mahmood; Jiang, Xian-Cheng; Jin, Weijun

    2015-01-01

    Site-1 protease (S1P) is the key enzyme required for activation of the sterol regulatory element binding proteins (SREBPs) that govern lipid synthesis. While S1P has been speculated to influence plasma apoB-containing lipoprotein (Blp) metabolism, there has been little investigative work. LDL receptor (LDLR) is the major receptor for clearing plasma LDL cholesterol (LDL-c). Proprotein convertase subtilisin kexin type 9 (PCSK9) modulates LDL-c through post-translational degradation of the LDLR. A hepatic-specific knockdown (KD) of S1P was achieved using floxed S1P mouse models (S1P(f/f) and LDLR(-/-)S1P(f/f)) and hepatic expression of Cre recombinase. Lipids were measured in total plasma and size fractionated plasma using colorimetric assays. Realtime polymerase chain reaction, western blotting and ELISA were used to determine hepatic expression of key genes/protein. Plasmid mediated overexpression and siRNA mediated knockdown of genes were performed in mouse primary hepatocytes to determine the mechanistic basis of PCSK9 gene regulation. A hepatic-specific KD of S1P resulted in a 45 % and 38 % reduction in plasma total cholesterol and triglyceride levels, respectively. Hepatic S1P KD had a minimal effect on plasma Blp cholesterol (Blp-c) in S1P(f/f) mice, despite significantly reducing VLDL secretion. Notably, hepatic S1P KD decreased the LDL receptor (LDLR) mRNA expression by 50 %. However, the reduction in LDLR protein levels was less than that of mRNA expression, especially under fed conditions. Further assessment of hepatic S1P deficiency revealed that it increased LDLR protein stability in vivo. Mechanistically, hepatic S1P KD was shown to decrease the liver and plasma levels of the protein proprotein convertase subtilisin/kexin type 9 (PCSK9), which degrades LDLR protein. This effect was more prominent in the fed condition and sufficient to account for the discordance in LDLR mRNA and protein levels. Furthermore, hepatic S1P was shown to regulate PCSK9

  5. Requirement of cholesterol for secretion of the very low density lipoprotein (VLDL) by the rat liver

    International Nuclear Information System (INIS)

    Khan, B.; Wilcox, H.G.; Elam, M.B.; Heimberg, M.

    1987-01-01

    Fatty acids stimulate hepatic secretion of VLDL triglyceride (TG) and cholesterol (C), increase C synthesis, and enhance activity of HMG-CoA reductase. Livers from normal fed male rats were perfused for 4 hr in a medium containing 20μCi [2- 14 C] acetate, 6g/dl serum albumin, 300 mg/dl glucose in Krebs-Henseleit HCO 3 buffer (pH 7.4), 0-100 μg/ml mevinolin, and oleate. TG secretion was decreased 0%, 23%, and 32% from control with 1, 10, and 100 μg/ml mevinolin, respectively; there was no significant effect on C or C ester (CE) secretion. Specific activity (dpm/μmol) of C synthesized from acetate in the liver decreased 67%, 98%, and 99% from control; incorporation into CE decreased 64%, 81%, and 84%, respectively. TG and phospholipid (PL) activities did not change. Synthesis of TG and PL from [1- 14 C] oleate by isolated hepatocytes from normal fed rats was not affected by addition of 0-100 μg/ml mevinolin. The mass of C and TG in the liver did not change. Preliminary experiments with perfused liver suggest that output of VLDL TG, C, CE, and PL was diminished; the ratio of C/TG and PL/TG in the VLDL was constant, suggesting secretion of fewer VLDL particles with the same composition. These data suggest that mevinolin acutely reduces biosynthesis of C and secretion of the VLDL, presumably because of a requirement of C for synthesis and secretion of the VLDL

  6. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of β-cell function in African American women.

    Science.gov (United States)

    Maturu, Amita; DeWitt, Peter; Kern, Philip A; Rasouli, Neda

    2015-05-01

    The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians. However, there are conflicting data on TG/HDL-C ratio as a predictor of IR in African Americans. Compared to Caucasians, African Americans have lower TG levels and increased insulin levels despite a greater risk for diabetes. We hypothesized that the TG/HDL-C ratio is predictive of IR and/or β-cell function in African American (AA) women. Non-diabetic AA women (n = 41) with a BMI > 25 kg/m(2) underwent frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin sensitivity (SI) and the acute insulin response to glucose (AIRg) were measured using minimal model and β-cell function was determined by disposition index (DI = S I*AIRg). IR was defined as the lowest tertile of SI ( 0.70 was defined as significant discrimination. The mean (± SD) age was 38.5 ± 11.3 years, with BMI of 33.5 ± 6.7 kg/m(2) and fasting glucose of 86.5 ± 10.5 mg/dL. The AUC-ROC for the prediction of DI women. However, we did show an inverse association between the TG/HDL-C ratio and β-cell function, suggesting that this simple tool may effectively identify AA women at risk for DM2. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease

    DEFF Research Database (Denmark)

    Frikke-Schmidt, R.; Nordestgaard, B.G.; Stene, M.C.A.

    2008-01-01

    increased risk of ischemic heart disease ( IHD). Design, Setting, and Participants Three studies of white individuals from Copenhagen, Denmark, were used: the Copenhagen City Heart Study ( CCHS), a 31-year prospective general population study ( n= 9022; 28 heterozygotes); the Copenhagen General Population...

  8. Significant Relationship Between Serum High-sensitivity C-Reactive Protein, High-density Lipoprotein Cholesterol Levels and Children With Kawasaki Disease and Coronary Artery Lesions

    Directory of Open Access Journals (Sweden)

    Chun-Yen Ou

    2009-09-01

    Conclusion: Our results support the possibility of ongoing low-grade inflammation late after the acute phase of KD in children with coronary aneurysms. Serum hs-CRP and HDL-C levels are associated with coronary artery lesions in children with KD.

  9. Changes in triglycerides and high-density lipoprotein cholesterol may precede peripheral insulin resistance, with 2-h insulin partially mediating this unidirectional relationship: a prospective cohort study.

    Science.gov (United States)

    Han, Tianshu; Cheng, Yu; Tian, Shuang; Wang, Li; Liang, Xi; Duan, Wei; Na, Lixin; Sun, Changhao

    2016-11-04

    Results of longitudinal researches regarding the temporal relationship between dyslipidemia and insulin resistance (IR) are inconsistent. This study assessed temporal relationships of blood lipids with IR and determined whether there are any mediating effects existed in these temporal relationships. This study examined a longitudinal cohort of 3325 subjects aged 20-74 years from China with an average of 4.2 years follow-up. Measurements of fasting blood lipids, as well as fasting and 2-h serum glucose and insulin, were obtained at two time points. The Gutt index and HOMA-IR were calculated as indicators of peripheral IR and hepatic IR. A cross-lagged path analysis was performed to examine the temporal relationships between blood lipids and IR. A mediation analysis was used to examine mediating effect. After adjusting for covariates, the cross-lagged path coefficients from baseline TG and HDL-C to follow-up Gutt index were significantly greater than those from baseline Gutt index to follow-up TG and HDL-C (β 1  = -0.131 vs β 2  = -0.047, P index with a 59.3% mediating effect for TG and 61.0% for HDL-C. These findings provide strong evidence that dyslipidemia probably precede peripheral IR and that 2-h insulin partially mediates this unidirectional temporal relationship.

  10. 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.

  11. Background diet and fat type alters plasma lipoprotein response but not aortic cholesterol accumulation in F1B Golden Syrian hamsters.

    Science.gov (United States)

    Dillard, Alice; Matthan, Nirupa R; Spartano, Nicole L; Butkowski, Ann E; Lichtenstein, Alice H

    2013-12-01

    Dietary modification alters plasma lipoprotein profiles and atherosclerotic lesion progression in humans and some animal models. Variability in response to diet induced atherosclerosis has been reported in hamsters. Assessed was the interaction between background diet composition and dietary fat type on aortic cholesterol accumulation, lipoprotein profiles, hepatic lipids and selected genes. F1B Golden Syrian hamsters (20/group) were fed (12 weeks) semi-purified or non-purified diets containing either 10 % (w/w) coconut oil or safflower oil and 0.15 % (w/w) cholesterol. The non-purified diets relative to semi-purified diets resulted in significantly higher TC (72 % [percent difference] and 38 %, coconut oil and safflower oil, respectively) and nHDL-C (84 and 61 %, coconut oil and safflower oil, respectively), and lower HDL-C (-47 and -45 %, coconut oil and safflower oil, respectively) concentrations. Plasma triacylglycerol concentrations in the hamsters fed the non-purified coconut oil-supplemented diets were three- to fourfold higher than non-purified safflower oil-supplemented, and both semi-purified diets. With the exception of HDL-C, a significant effect of fat type was observed in TC, nHDL-C and triacylglycerol (all P < 0.05) concentrations. Regardless of diet induced differences in lipoprotein profiles, there was no significant effect on aortic cholesterol accumulation. There was an inverse relationship between plasma nHDL-C and triacylglycerol, and hepatic cholesteryl ester content (P < 0.001). Diet induced differences in hepatic gene transcription (LDL receptor, apoB-100, microsomal transfer protein) were not reflected in protein concentrations. Although hamsters fed non-purified and/or saturated fatty acid-supplemented diets had more atherogenic lipoprotein profiles compared to hamsters fed semi-purified and/or polyunsaturated fatty acid-supplemented diets these differences were not reflected in aortic cholesterol accumulation.

  12. 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...

  13. 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

  14. 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.

  15. Homozygous missense mutation (G56R in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1 in two siblings with fasting chylomicronemia (MIM 144650

    Directory of Open Access Journals (Sweden)

    Hegele Robert A

    2007-09-01

    Full Text Available Abstract Background Mice with a deleted Gpihbp1 gene encoding glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1 develop severe chylomicronemia. We screened the coding regions of the human homologue – GPIHBP1 – from the genomic DNA of 160 unrelated adults with fasting chylomicronemia and plasma triglycerides >10 mmol/L, each of whom had normal sequence of the LPL and APOC2 genes. Results One patient with severe type 5 hyperlipoproteinemia (MIM 144650, fasting chylomicronemia and relapsing pancreatitis resistant to standard therapy was found to be homozygous for a novel GPIHBP1 missense variant, namely G56R. This mutation was absent from the genomes of 600 control subjects and 610 patients with hyperlipidemia. The GPIHBP1 G56 residue has been conserved throughout evolution and the G56R mutation was predicted to have compromised function. Her homozygous brother also had refractory chylomicronemia and relapsing pancreatitis together with early coronary heart disease. G56R heterozygotes in the family had fasting mild hypertriglyceridemia. Conclusion Thus, a very rare GPIHBP1 missense mutation appears to be associated with severe hypertriglyceridemia and chylomicronemia.

  16. A Cross-Sectional Study Demonstrating Increased Serum Amyloid A Related Inflammation in High-Density Lipoproteins from Subjects with Type 1 Diabetes Mellitus and How This Association Was Augmented by Poor Glycaemic Control

    Directory of Open Access Journals (Sweden)

    Jane McEneny

    2015-01-01

    Full Text Available Inflammatory atherosclerosis is increased in subjects with type 1 diabetes mellitus (T1DM. Normally high-density lipoproteins (HDL protect against atherosclerosis; however, in the presence of serum amyloid-A- (SAA- related inflammation this property may be reduced. Fasting blood was obtained from fifty subjects with T1DM, together with fifty age, gender and BMI matched control subjects. HDL was subfractionated into HDL2 and HDL3 by rapid ultracentrifugation. Serum-hsCRP and serum-, HDL2-, and HDL3-SAA were measured by ELISAs. Compared to control subjects, SAA was increased in T1DM subjects, nonsignificantly in serum (P=0.088, and significantly in HDL2(P=0.003 and HDL3(P=0.005. When the T1DM group were separated according to mean HbA1c (8.34%, serum-SAA and HDL3-SAA levels were higher in the T1DM subjects with HbA1c ≥ 8.34%, compared to when HbA1c was 0.05. This cross-sectional study demonstrated increased SAA-related inflammation in subjects with T1DM that was augmented by poor glycaemic control. We suggest that SAA is a useful inflammatory biomarker in T1DM, which may contribute to their increased atherosclerosis risk.

  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. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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...

  3. Remnant lipoproteins.

    Science.gov (United States)

    Varbo, Anette; Nordestgaard, Børge G

    2017-08-01

    To review recent advances in the field of remnant lipoproteins and remnant cholesterol with a focus on cardiovascular disease risk. In line with previous years' research, current observational, genetic, and mechanistic studies find remnant lipoproteins (defined in different ways) to be involved in atherosclerosis development and cardiovascular disease risk. High concentrations of remnant cholesterol could explain some of the residual risk of cardiovascular disease seen after LDL cholesterol lowering. This will be increasingly important as populations worldwide become more obese and more have diabetes, both of which elevate remnant cholesterol concentrations. Many smaller scale studies and post hoc analyses show that remnant cholesterol can be lowered by different types of drugs; however, results from large scale studies with the primary aim of reducing cardiovascular disease risk through lowering of remnant cholesterol in individuals with elevated concentrations are still missing, although some are under way. Remnant cholesterol is a risk factor for cardiovascular disease, and can be lowered by different types of drugs; however, large scale studies of cardiovascular disease risk reduction through remnant lipoprotein lowering are under way.

  4. Acute and chronic effects of a 24-hour intravenous triglyceride emulsion challenge on plasma lecithin : cholesterol acyltransferase, phospholipid transfer protein, and cholesteryl ester transfer protein activities

    NARCIS (Netherlands)

    Riemens, SC; Van Tol, A; Sluiter, WJ; Dullaart, RPF

    Lecithin:cholesterol acyltransferase (LCAT), phospholipid transfer protein (PLTP), and cholesteryl ester transfer protein (CETP) are key factors in remodeling of high density lipoproteins (HDL) and triglyceride-rich lipoproteins. We examined the effect of a large, 24 h intravenous fat load on plasma

  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. 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

  7. Comparison of apolipoprotein (apoB/apoA-I and lipoprotein (total cholesterol/HDL ratio determinants. Focus on obesity, diet and alcohol intake.

    Directory of Open Access Journals (Sweden)

    Gianluca Tognon

    Full Text Available The ratio between apolipoprotein B and apolipoprotein A-I (apoB/apoA-I has been suggested to be a powerful and more accurate predictor of future cardiovascular disease risk than total cholesterol and HDL cholesterol. Since diet and lifestyle can directly influence dyslipidemia, it is of interest to identify modifiable factors that are associated with high levels of the apolipoprotein ratio and if they can have a different association with a more traditional indicator of cardiovascular risk such as total cholesterol/HDL. The relationship between obesity and dyslipidemia is established and it is of interest to determine which factors can modify this association. This study investigated the cross-sectional association of obesity, diet and lifestyle factors with apoB/apoA-I and total cholesterol/HDL respectively, in a Swedish population of 2,907 subjects (1,537 women as part of the INTERGENE study. The apolipoprotein and lipoprotein ratios were highly correlated, particularly in women, and obesity was strongly associated with both. Additionally, age, cigarette smoking and alcohol intake were important determinants of these ratios. Alcohol was the only dietary factor that appreciably attenuated the association between obesity and each of the ratios, with a stronger attenuation in women. Other dietary intake and lifestyle-related factors such as smoking status and physical activity had a lower effect on this association. Because the apolipoprotein and lipoprotein ratios share similar diet and lifestyle determinants as well as being highly correlated, we conclude that either of these ratios may be a sufficient indicator of dyslipidemia.

  8. Probucol selectively increases oxidation of atherogenic lipoproteins in cholesterol-fed mice and in Watanabe heritable hyperlipidemic rabbits

    DEFF Research Database (Denmark)

    Lauridsen, S.T.; Mortensen, Alicja

    1999-01-01

    The anti-atherogenic and cholesterol-lowering drug probucol (0.5-1%) or quercetin (1%), a natural antioxidant, was given to cholesterol-fed (1.5%) mice for a period of 6 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for a period of 8 weeks to investigate the oxidative changes.......001) and cholesterol-fed mice (579.7 +/- 47.3 nmol/g vs. 408.1 +/- 85.8 nmol/g, P mice: P ... and thereby leads to a decrease in cholesterol levels....

  9. 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.

  10. 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.

  11. Scavenger Receptor Class B Type I Mediates Biliary Cholesterol Secretion Independent of ATP-Binding Cassette Transporter g5/g8 in Mice

    NARCIS (Netherlands)

    Wiersma, Harmen; Gatti, Alberto; Nijstad, Niels; Elferink, Ronald P. J. Oude; Kuipers, Folkert; Tietge, Uwe J. F.

    2009-01-01

    Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesterol from high-density lipoprotein (HDL) particles by the liver and influences biliary cholesterol secretion. However, it is not dear, if this effect is direct or indirect. The aim of this study was to determine the impact

  12. Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol

    NARCIS (Netherlands)

    A. Grefhorst (Aldo); D.M. Oosterveer (Daniella); G. Brufau (Gemma); M. Boesjes (Marije); F. Kuipers (Folkert); A. Groen (Albert)

    2012-01-01

    textabstractObjective: Pharmacological LXR activation has anti-atherosclerotic actions in animal models. Part of these beneficial effects may be explained by accelerated reverse cholesterol transport since both plasma high density lipoprotein (HDL) cholesterol and fecal neutral sterol secretion are

  13. Pharmacological LXR activation reduces presence of SR-B1 in liver membranes contributing to LXR-mediated induction of HDL-cholesterol

    NARCIS (Netherlands)

    Grefhorst, Aldo; Oosterveer, Maaike H.; Brufau, Gemma; Boesjes, Marije; Kuipers, Folkert; Groen, Albert K.

    Objective: Pharmacological LXR activation has anti-atherosclerotic actions in animal models. Part of these beneficial effects may be explained by accelerated reverse cholesterol transport since both plasma high density lipoprotein (HDL) cholesterol and fecal neutral sterol secretion are higher upon

  14. 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...

  15. Mutations in the gene for lipoprotein lipase. A cause for low HDL cholesterol levels in individuals heterozygous for familial hypercholesterolemia

    NARCIS (Netherlands)

    Pimstone, S. N.; Gagné, S. E.; Gagné, C.; Lupien, P. J.; Gaudet, D.; Williams, R. R.; Kotze, M.; Reymer, P. W.; Defesche, J. C.; Kastelein, J. J.

    1995-01-01

    Familial hypercholesterolemia (FH) is characterized by elevated plasma concentrations of LDL cholesterol resulting from mutations in the gene for the LDL receptor. Low HDL cholesterol levels are seen frequently in patients both heterozygous and homozygous for mutations in this gene. Suggested

  16. 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.

  17. 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

  18. 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

  19. 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

  20. Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans

    NARCIS (Netherlands)

    Brunham, Liam R.; Tietjen, Ian; Bochem, Andrea E.; Singaraja, Roshni R.; Franchini, Patrick L.; Radomski, Chris; Mattice, Maryanne; Legendre, Annick; Hovingh, G. Kees; Kastelein, John J. P.; Hayden, Michael R.

    2011-01-01

    The scavenger receptor class B, member 1 (SR-BI), is a key cellular receptor for high-density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR-BI and high HDL cholesterol (HDL-C).

  1. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    Science.gov (United States)

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C l...

  2. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    DEFF Research Database (Denmark)

    Zanoni, Paolo; Khetarpal, Sumeet A; Larach, Daniel B

    2016-01-01

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-...

  3. 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.

  4. Dietary carbohydrate modifies the inverse association between saturated fat intake and cholesterol on very low-density lipoproteins

    Science.gov (United States)

    We aimed to investigate the relationship between dietary saturated fat on fasting triglyceride (TG) and cholesterol levels, and any mediation of this relationship by dietary carbohydrate intake. Men and women in the NHLBI Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN) study (n = 1036, mea...

  5. 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.

  6. Antioxidant status, lipoprotein profile and liver lipids in rats fed on high-cholesterol diet containing currant oil rich in n-3 and n-6 polyunsaturated fatty acids.

    Science.gov (United States)

    Vecera, R; Skottová, N; Vána, P; Kazdová, L; Chmela, Z; Svagera, Z; Walterá, D; Ulrichová, J; Simánek, V

    2003-01-01

    Plant-based n-3 polyunsaturated fatty acids (PUFA) possess a prospective antiatherogenic potential. Currant oil from Ribes nigrum L. is one of the few plant oils containing PUFAn-3 (15.3 mol%) in addition to PUFAn-6 (60.5 mol%). This study was aimed at comparing the effects of currant oil with those of lard fat, rich in saturated (43.8 mol%) and monounsaturated (47.0 mol%) fatty acids, on antioxidant parameters, the lipoprotein profile and liver lipids in rats fed on 1 % (w/w) cholesterol diets containing either 10 % of currant oil (COD) or lard fat (LFD). After 3 weeks of feeding, the COD induced a significant decrease in blood glutathione (GSH) and an increase in Cu(2+) induced oxidizability of serum lipids, but did not affect liver GSH and t-butyl hydroperoxide-induced lipoperoxidation of liver microsomes. Although the COD did not cause accumulation of liver triacylglycerols as LFD, the lipoprotein profile (VLDL, LDL, HDL) was not significantly improved after COD. The consumption of PUFAn-3 was reflected in LDL as an increase in eicosapentaenoic and docosahexaenoic acid. These results suggest that currant oil affects positively the lipid metabolism in the liver, above all it does not cause the development of a fatty liver. However, adverse effects of currant oil on the antioxidant status in the blood still remain of concern.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. How much does HDL cholesterol add to risk estimation? A report from the SCORE Investigators.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2009-06-01

    Systematic COronary Risk Evaluation (SCORE), the risk estimation system recommended by the European guidelines on cardiovascular disease prevention, estimates 10-year risk of cardiovascular disease mortality based on age, sex, country of origin, systolic blood pressure, smoking status and either total cholesterol (TC) or TC\\/high-density lipoprotein cholesterol (HDL-C) ratio. As, counterintuitively, these two systems perform very similarly, we have investigated whether incorporating HDL-C and TC as separate variables improves risk estimation.

  13. 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.

  14. 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.

  15. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas

    2012-01-01

    , S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...... was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies......Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...

  16. 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

  17. 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.

  18. 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.

  19. Characteristics of human hypo- and hyperresponders to dietary cholesterol.

    Science.gov (United States)

    Katan, M B; Beynen, A C

    1987-03-01

    The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

  20. Increased Hepatic Expression of Endothelial Lipase Inhibits Cholesterol Diet-Induced Hypercholesterolemia and Atherosclerosis in Transgenic Rabbits.

    Science.gov (United States)

    Wang, Chuan; Nishijima, Kazutoshi; Kitajima, Shuji; Niimi, Manabu; Yan, Haizhao; Chen, Yajie; Ning, Bo; Matsuhisa, Fumikazu; Liu, Enqi; Zhang, Jifeng; Chen, Y Eugene; Fan, Jianglin

    2017-07-01

    Endothelial lipase (EL) is a key determinant in plasma high-density lipoprotein-cholesterol. However, functional roles of EL on the development of atherosclerosis have not been clarified. We investigated whether hepatic expression of EL affects plasma lipoprotein metabolism and cholesterol diet-induced atherosclerosis. We generated transgenic (Tg) rabbits expressing the human EL gene in the liver and then examined the effects of EL expression on plasma lipids and lipoproteins and compared the susceptibility of Tg rabbits with cholesterol diet-induced atherosclerosis with non-Tg littermates. On a chow diet, hepatic expression of human EL in Tg rabbits led to remarkable reductions in plasma levels of total cholesterol, phospholipids, and high-density lipoprotein-cholesterol compared with non-Tg controls. On a cholesterol-rich diet for 16 weeks, Tg rabbits exhibited significantly lower hypercholesterolemia and less atherosclerosis than non-Tg littermates. In Tg rabbits, gross lesion area of aortic atherosclerosis was reduced by 52%, and the lesions were characterized by fewer macrophages and smooth muscle cells compared with non-Tg littermates. Increased hepatic expression of EL attenuates cholesterol diet-induced hypercholesterolemia and protects against atherosclerosis. © 2017 American Heart Association, Inc.

  1. Lipoprotein cholesterol fractions are related to markers of inflammation in children and adolescents with juvenile idiopathic arthritis

    DEFF Research Database (Denmark)

    Bohr, Anna-Helene; Pedersen, Freddy Karup; Nielsen, Claus Henrik

    2016-01-01

    disease activity (JADAS27), biomarkers of inflammation (myelo-related protein complex 8/14 (MRP8/14), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR)), body mass index (BMI), waist-to-height ratio (WtH ratio), and PA were explored. RESULTS: Mean values for TC, LDLc, and HDLc...... in the patients were within the normal range for Danish Children. HDLc was negatively correlated with MRP8/14 (r = -0.343, CI -0.474 to -0.201, p MRP8/14 correlated positively...... with CRP, JADAS27 and WtH ratio (r = 0.277, CI 0.142 to 0.413, p = 0.001). CONCLUSIONS: Levels of cholesterol fractions in patients with JIA were found within the normal range. Nonetheless, the level of HDLc was negatively associated with the level of the inflammatory marker MRP8/14, which is in accordance...

  2. 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.

  3. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  4. 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

  5. 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.

  6. 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.

  7. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Zaater, M.K.

    2011-01-01

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  8. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    International Nuclear Information System (INIS)

    Schreiber, J.R.; Nakamura, K.; Schmit, V.; Weinstein, D.B.

    1984-01-01

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125 I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125 I-monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production

  9. 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).

  10. 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

  11. Lipoprotein complex formation

    International Nuclear Information System (INIS)

    Musliner, T.A.; Krauss, R.M.

    1987-01-01

    Transfers of lipids and proteins between different lipoproteins are known to occur in the course of their metabolism. It is likely that these transfers take place during transient physical associations between lipoprotein particles, but the nature and chemical basis for such interactions are poorly understood. The fact that lipid and apolipoprotein movements are particularly prevalent during the intravascular lipolysis of triglyceride-rich lipoproteins suggested to us that lipolysis products accumulating on these particles might promote physical binding with other lipoproteins. To test this hypothesis, we studied interactions between very low-density, low density, and high-density lipoproteins in the setting of partial lipolysis by bovine milk lipoprotein lipase in the presence of limited unesterified fatty acid acceptor. 2 figs., 1 tab

  12. 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

  13. The effects of ABCG5/G8 polymorphisms on plasma HDL cholesterol concentrations depend on smoking habit in the Boston Puerto Rican Health Study

    Science.gov (United States)

    Background-Low high-density lipoprotein cholesterol (HDL-C) is associated with an increased risk for atherosclerosis and concentrations are modulated by genetic and environmental factors such as smoking. Objective- To assess whether the association of common single nucleotide polymorphisms (SNPs...

  14. Effect of growth hormone replacement therapy on plasma lecithin : cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

    NARCIS (Netherlands)

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

    The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, We unknown. We carried out a 6 mouths study in 24

  15. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

    NARCIS (Netherlands)

    de Munter, J.S.L.; van Valkengoed, I.G.; Stronks, K.; Agyemang, C.

    2011-01-01

    ABSTRACT: BACKGROUND: Evidence suggests that physical activity (PA) has a beneficial effect on high-density lipoprotein cholesterol (HDL) and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due

  16. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

    NARCIS (Netherlands)

    de Munter, Jeroen S. L.; van Valkengoed, Irene G.; Stronks, Karien; Agyemang, Charles

    2011-01-01

    Evidence suggests that physical activity (PA) has a beneficial effect on high-density lipoprotein cholesterol (HDL) and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the

  17. 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 ri