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Sample records for cholesterol ldl

  1. LDL Cholesterol Test

    Science.gov (United States)

    ... products and services. Advertising & Sponsorship: Policy | Opportunities LDL Cholesterol Share this page: Was this page helpful? Also ... LDL; LDL-C Formal name: Low-Density Lipoprotein Cholesterol Related tests: Cholesterol ; HDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  2. LDL cholesterol: controversies and future therapeutic directions.

    Science.gov (United States)

    Ridker, Paul M

    2014-08-16

    Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

  3. [Comparison of calculated LDL cholesterol (LDL-C) versus measured LDL cholesterol (LDL-M) and potential impact in terms of therapeutic management].

    Science.gov (United States)

    Reignier, Arnaud; Sacchetto, Emilie; Hardouin, Jean-Benoît; Orsonneau, Jean-Luc; Le Carrer, Didier; Delaroche, Odile; Bigot-Corbel, Edith

    2014-01-01

    LDL-cholesterol value is one of the criteria used by the Haute autorité de santé (HAS) in the management of patients in primary and secondary prevention with the aim to reduce cardiovascular mortality. In this respect, the recommendations have been established based on target to achieve LDL-cholesterol. Currently in France, the determination of LDL-cholesterol is mainly carried out by the Friedewald formula whose limits are well known. However, reliable methods for the determination of LDL-cholesterol exist. We compared the results of calculated and measured LDL-cholesterol obtained from 444 patients presenting normal triglyceridemia values in terms of ranking relative to the thresholds of the HAS. The correlation between the two methods is quite good, but a significant difference (p <0.0001) was observed between the calculated and measured values of LDL-cholesterol. On the other hand in 17% of cases the classification of subjects will be different, with a majority so overestimation of calculated LDL-cholesterol with respect to measured LDL-cholesterol. This overestimation is not proportional, in fact most values measured LDL-cholesterol, the higher the calculate-measured difference is important. The rating difference is particularly important when subjects have between 1 and 3 factors of cardiovascular risk where the target LDL-cholesterol to achieve is between 1.3 and 1.9 g/L. The management of patients with lipid lowering may potentially be dependent on the method used for the determination of LDL-cholesterol.

  4. Empagliflozin, via Switching Metabolism Toward Lipid Utilization, Moderately Increases LDL Cholesterol Levels Through Reduced LDL Catabolism.

    Science.gov (United States)

    Briand, François; Mayoux, Eric; Brousseau, Emmanuel; Burr, Noémie; Urbain, Isabelle; Costard, Clément; Mark, Michael; Sulpice, Thierry

    2016-07-01

    In clinical trials, a small increase in LDL cholesterol has been reported with sodium-glucose cotransporter 2 (SGLT2) inhibitors. The mechanisms by which the SGLT2 inhibitor empagliflozin increases LDL cholesterol levels were investigated in hamsters with diet-induced dyslipidemia. Compared with vehicle, empagliflozin 30 mg/kg/day for 2 weeks significantly reduced fasting blood glucose by 18%, with significant increase in fasting plasma LDL cholesterol, free fatty acids, and total ketone bodies by 25, 49, and 116%, respectively. In fasting conditions, glycogen hepatic levels were further reduced by 84% with empagliflozin, while 3-hydroxy-3-methylglutaryl-CoA reductase activity and total cholesterol hepatic levels were 31 and 10% higher, respectively (both P catabolism of (3)H-cholesteryl oleate-labeled LDL injected intravenously by 20%, indicating that empagliflozin raises LDL levels through reduced catabolism. Unexpectedly, empagliflozin also reduced intestinal cholesterol absorption in vivo, which led to a significant increase in LDL- and macrophage-derived cholesterol fecal excretion (both P < 0.05 vs. vehicle). These data suggest that empagliflozin, by switching energy metabolism from carbohydrate to lipid utilization, moderately increases ketone production and LDL cholesterol levels. Interestingly, empagliflozin also reduces intestinal cholesterol absorption, which in turn promotes LDL- and macrophage-derived cholesterol fecal excretion.

  5. The effect of lowering LDL cholesterol on vascular access patency

    DEFF Research Database (Denmark)

    Herrington, William; Emberson, Jonathan; Staplin, Natalie

    2014-01-01

    BACKGROUND AND OBJECTIVES: Reducing LDL cholesterol (LDL-C) with statin-based therapy reduces the risk of major atherosclerotic events among patients with CKD, including dialysis patients, but the effect of lowering LDL-C on vascular access patency is unclear. DESIGN, SETTING, PARTICIPANTS...

  6. LDL cholesterol still a problem in old age?

    DEFF Research Database (Denmark)

    Postmus, Iris; Deelen, Joris; Sedaghat, Sanaz

    2015-01-01

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

  7. Discordance of Non-HDL and Directly Measured LDL Cholesterol: Which Lipid Measure is Preferred When Calculated LDL Is Inaccurate?

    OpenAIRE

    Lawrence Baruch; Chiong, Valerie J.; Sanjay Agarwal; Bhanu Gupta

    2013-01-01

    Objective. To determine if non-HDL cholesterol (N-HDL) and directly measured LDL cholesterol (D-LDL) are clinically equivalent measurements. Patients and Methods. Eighty-one subjects recruited for 2 cholesterol treatment studies had at least 1 complete fasting lipid panel and D-LDL performed simultaneously; 64 had a second assessment after 4 to 6 weeks, resulting in 145 triads of C-LDL, D-LDL, and N-HDL. To directly compare N-HDL to D-LDL and C-LDL, we normalized the N-HDL by subtracting 30 f...

  8. Effects of Lowering LDL Cholesterol on Progression of Kidney Disease

    DEFF Research Database (Denmark)

    Haynes, Richard; Lewis, David; Emberson, Jonathan

    2014-01-01

    Lowering LDL cholesterol reduces the risk of developing atherosclerotic events in CKD, but the effects of such treatment on progression of kidney disease remain uncertain. Here, 6245 participants with CKD (not on dialysis) were randomly assigned to simvastatin (20 mg) plus ezetimibe (10 mg) daily...... or matching placebo. The main prespecified renal outcome was ESRD (defined as the initiation of maintenance dialysis or kidney transplantation). During 4.8 years of follow-up, allocation to simvastatin plus ezetimibe resulted in an average LDL cholesterol difference (SEM) of 0.96 (0.02) mmol/L compared...... with placebo; rate ratio, 0.93; 95% CI, 0.86 to 1.01; P=0.09). Exploratory analyses also showed no significant effect on the rate of change in eGFR. Lowering LDL cholesterol by 1 mmol/L did not slow kidney disease progression within 5 years in a wide range of patients with CKD....

  9. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus).

    Science.gov (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood

    2013-02-01

    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  10. Reducing elevated plasma LDL cholesterol: the central role of the LDL receptor.

    Science.gov (United States)

    Vincent, J

    2014-07-01

    Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and reduction of elevated LDL-C reduces mortality in patients at risk. This benefit has evolved from the use of statins and knowledge of the LDL receptor (LDLR). The most potent drugs used for dyslipidemias act by mechanisms that involve this receptor. Advances in molecular genetics and understanding of the regulation of this receptor have revealed several pharmacological targets that are being explored to develop more targeted therapies for dyslipidemias.

  11. LDL cholesterol goals and cardiovascular risk during statin treatment

    DEFF Research Database (Denmark)

    Olsson, Anders G; Lindahl, Christina; Holme, Ingar

    2011-01-01

    We assessed the proportion of patients treated with either simvastatin 20 or 40 mg or atorvastatin 80 mg who achieved low-density lipoprotein cholesterol (LDL-C) goals of 2.5 or 2.0 mmol/l in the Incremental Decrease in End Points Through Aggressive Lipid Lowering (IDEAL) study. We explored how...

  12. Discordance of Non-HDL and Directly Measured LDL Cholesterol: Which Lipid Measure is Preferred When Calculated LDL Is Inaccurate?

    Science.gov (United States)

    Baruch, Lawrence; Chiong, Valerie J; Agarwal, Sanjay; Gupta, Bhanu

    2013-01-01

    Objective. To determine if non-HDL cholesterol (N-HDL) and directly measured LDL cholesterol (D-LDL) are clinically equivalent measurements. Patients and Methods. Eighty-one subjects recruited for 2 cholesterol treatment studies had at least 1 complete fasting lipid panel and D-LDL performed simultaneously; 64 had a second assessment after 4 to 6 weeks, resulting in 145 triads of C-LDL, D-LDL, and N-HDL. To directly compare N-HDL to D-LDL and C-LDL, we normalized the N-HDL by subtracting 30 from the N-HDL (N-HDLA). Results. There was significant correlation between N-HDLA, D-LDL, and C-LDL. Correlation was significantly greater between N-HDLA and C-LDL than between N-HDLA and D-LDL. A greater than 20 mg/dL difference between measures was observed more commonly between N-HDLA and D-LDL, 29%, than between C-LDL and N-HDLA, 11% (P LDL and D-LDL, 17% (P = 0.028). Clinical discordance was most common, and concordance was least common between N-HDL and D-LDL. Conclusions. Our findings suggest that N-HDL cholesterol and D-LDL cholesterol are not clinically equivalent and frequently discordant. As N-HDL may be superior to even C-LDL for predicting events in statin-treated patients, utilizing N-HDL to guide therapy would appear to be preferable to D-LDL when C-LDL is inaccurate.

  13. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus : Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  14. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    P.J.W.H. Kappelle; G.M. Dallinga-Thie; R.P.F. Dullaart

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  15. LDL Cholesterol, Statins And PCSK 9 Inhibitors

    Science.gov (United States)

    Gupta, Sanjiv

    2015-01-01

    Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20–30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated. For homozygous familial hypercholesterolemia (HOFH), a microsomal triglyceride transfer protein MTP inhibitor (Lopitamide) and antisense oligonucleotide (ASO) (Mipomersen) have recently been approved by FDA, USA through ‘Risk evaluation and Mitigation Strategy (REMS)’. Possible future therapies include PCSK-9 inhibitors which have excellent lipid lowering properties. Three monoclonal antibodies (PCSK 9 Inhibitors) alirocumab, evolocumab and Bococizumab are under advanced clinical stage IV trials and awaiting approval by FDA and European Medicines Agency. PMID:26432726

  16. [A simple test for quantitative determination of LDL-cholesterol].

    Science.gov (United States)

    Mertz, D P; Thuilot, G

    1986-05-01

    The subject of the report is a novel precipitation test for the quantitative recording of LDL cholesterol based on the precipitation of LDL by dextran sulphate. Parallel assays of LDL cholesterol according to the new method and using quantitative lipoprotein electrophoresis as reference showed the results, in terms of the individual values and collectively, to be practically identical for a wide concentration range of various lipids and lipoproteins in the serum. The concentration ratio of the means obtained according to the two methods is 1.014 +/- 0.102 (standard deviation). The regression function displays a correlation coefficient of 0.9470. Double assays with the new technique yield a variation coefficient of 1.7 +/- 0.4%. Limitations of the method, which are insignificant for application in practice, are pointed out. The new precipitation method is simple, safe and useful for the quantitative estimation of the LDL cholesterol concentration in freshly obtained human serum. The method requires only little time and equipment.

  17. Agreement between fasting and postprandial LDL cholesterol measured with 3 methods in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lund, Søren S.; Petersen, Martin; Frandsen, Merete;

    2011-01-01

    LDL cholesterol (LDL-C) is a modifiable cardiovascular disease risk factor. We used 3 LDL-C methods to study the agreement between fasting and postprandial LDL-C in type 2 diabetes (T2DM) patients.......LDL cholesterol (LDL-C) is a modifiable cardiovascular disease risk factor. We used 3 LDL-C methods to study the agreement between fasting and postprandial LDL-C in type 2 diabetes (T2DM) patients....

  18. Nitric oxide-mediated endothlium-dependent vasodilation is impaired with borderline high-LDL cholesterol.

    Science.gov (United States)

    Diehl, Kyle J; Stauffer, Brian L; Greiner, Jared J; Weil, Brian R; DeSouza, Christopher A

    2012-02-01

    The experimental aims of this study were to determine: (1) whether nitric oxide-mediated endothelium-dependent vasodilation is blunted in adult humans with borderline high plasma low-density lipoprotein (LDL)-cholesterol compared with adults with optimal/near optimal LDL-cholesterol levels; and, if so: (2) whether the magnitude of impairment in adults with borderline high LDL-cholesterol is similar to adults with high LDL-cholesterol. Forearm blood flow responses to intraarterial infusions of acetylcholine and sodium nitroprusside were measured in 50 middle-aged (43-64 year) adults: 20 in the optimal/near optimal LDL-cholesterol range (<130 mg/dL); 20 with borderline high LDL-cholesterol (130-159 mg/dL); and 10 with high LDL-cholesterol ($160 mg/dL). In addition, blood flow responses to acetylcholine were determined in the absence and presence of the endothelial nitric oxide synthase inhibitor N(G) -monomethyl-L-arginine (L-NMMA). Vasodilation to acetylcholine was ~20% lower (p < 0.05) in the borderline high (from 4.3 ± 0.2 to 12.3 ± 0.8 mL/100 mL tissue/min) and high (from 4.3 ± 0.3 to 12.0 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol groups compared with the optimal/near optimal (from 4.4 ± 0.2 to 14.5 ± 0.5 mL/100 mL tissue/min) LDL-cholesterol group. L-NMMA significantly reduced (~30%) the vasodilator response to acetylcholine in the optimal/near optimal LDL-cholesterol group but not the borderline high or high LDL-cholesterol groups. Borderline high LDL-cholesterol is associated with impaired nitric oxide-mediated endothelium-dependent vasodilation.

  19. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates

    DEFF Research Database (Denmark)

    Lindholm, Marie W; Elmén, Joacim; Fisker, Niels;

    2012-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two ...

  20. Coenzyme O*U1*UO, Alpha-Tocopherol and Free Cholesterol in HDL and LDL Fractions

    DEFF Research Database (Denmark)

    Johansen, Kurt; Theorell, Henning; Karlsson, Jan;

    1991-01-01

    Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL......Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL...

  1. Low serum LDL cholesterol levels are associated with elevated mortality from liver cancer in Japan: the Ibaraki Prefectural health study.

    Science.gov (United States)

    Saito, Nobue; Sairenchi, Toshimi; Irie, Fujiko; Iso, Hiroyasu; Iimura, Kyoko; Watanabe, Hiroshi; Muto, Takashi; Ota, Hitoshi

    2013-01-01

    Liver cancer a global public health concern and well known for poor prognosis. The association between low total cholesterol level and liver cancer has been reported. However, the association between low low-density lipoprotein (LDL) cholesterol levels and liver cancer is still unclear. The aim of this study was to examine the relationship between LDL cholesterol level and liver cancer mortality. A total of 16,217 persons (5,551 men and 10,666 women) aged 40-79 years in 1993 were followed until 2008. LDL cholesterol levels were divided into four categories (LDL cholesterol level for liver cancer mortality was calculated using a multivariable Cox proportional hazards model. Covariates were age, sex, alanine transaminase, body mass index, alcohol intake and smoking status, all of which were correlated with LDL cholesterol levels. There were 51 deaths (32 men and 19 women) from liver cancer. Multivariable hazard ratios of liver cancer deaths for LDL cholesterol levels of LDL cholesterol levels of 80-99 mg/dl was 1.03 (95% CI: 0.42, 2.53), and for LDL cholesterol levels of ≥120 mg/dl was 0.43 (95% CI: 0.20, 0.92) compared with LDL cholesterol levels of 100-199 mg/dl (p for trendLDL cholesterol levels are associated with elevated risk of liver cancer mortality. Low LDL cholesterol may be a predictive marker for death due to liver cancer.

  2. Comparison of LDL- Cholesterol Enzymatic Method with Friedewald’s Formula

    Directory of Open Access Journals (Sweden)

    Hamidreza Yazdi (PhD

    2015-10-01

    Full Text Available Background and Objectives: Concentration low-density lipoprotein (LDL is one of the strongest indicators of atherosclerosis and predicts the diagnosis of cardiovascular diseases. LDL measurement accuracy is very important. LDL can be measured directly, such as enzymatic and nephelometry methods or can be calculated using Friedewald's formula. Despite the development of enzymatic methods and LDL nephelometry still in most laboratories is calculated using Friedewald's formula. The aim of this study was an investigation of correlation coefficient between two methods of measuring LDL- cholesterol levels. Methods: This descriptive cross-sectional study, performed on the 1141 patients. Cholesterol, triglycerides, HDL, LDL all patients assayed by enzymatic method. For patients with triglyceride levels of less than 400 mg/dl had LDL levels were calculated by Friedewald's formula. Normal levels of LDL/HDL ratio of less than 3.5 were considered. Results: Of the 1141 patients participating in this study, 38.3 % men and 61.7 % women. The mean patient age was 46.3 ± 16.1 years. Mean serum cholesterol, triglycerides and HDL were 177.9 ± 41.1, 132.9 ± 73.2 and 45.8 ± 13.2 mg/dl, respectively. Average direct and calculated LDL concentration was 82.1 ± 23.1 and 105.5 ± 35.8, respectively. The direct measurement of LDL, LDL/HDL levels in 97.1% of cases was normal, while 85.1 % of the calculation of LDL were normal. Pearson correlation coefficients were obtained by two methods: 0.869 (p <0.001. Conclusion: Despite the favorable correlation between two methods of measurements of LDL, the results of a calculation method is more than direct method. This can have a negative impact on the judgment of the treating physician. Key words: LDL, Enzymatic Method, Friedewald's Formula.

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

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  4. Postpartum weight retention is associated with elevated ratio of oxidized LDL lipids to HDL-cholesterol.

    Science.gov (United States)

    Puhkala, Jatta; Luoto, Riitta; Ahotupa, Markku; Raitanen, Jani; Vasankari, Tommi

    2013-12-01

    Oxidized LDL lipids (ox-LDL) are associated with lifestyle diseases such as cardiovascular diseases, metabolic syndrome and type 2 diabetes. The present study investigated how postpartum weight retention effects on ox-LDL and serum lipids. The study is a nested comparative research of a cluster-randomized controlled trial, NELLI (lifestyle and counselling during pregnancy). During early pregnancy (8-12 weeks) and 1 year postpartum, 141 women participated in measurements for determining of plasma lipids: total cholesterol (T-C), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triacylglycerols (TAG) and ox-LDL. Subjects were stratified into tertiles (weight loss, unaltered weight and weight gain groups) based on their weight change from baseline to follow-up. Ox-LDL was determined by baseline level of conjugated dienes in LDL lipids. Among the group of weight gainers, concentration of TAG reduced less (-0.14 vs. -0.33, p = 0.002), HDL-C reduced more (-0.31 vs. -0.16, p = 0.003) and ox-LDL/HDL-C ratio increased (3.0 vs. -0.2, p = 0.003) when compared to group of weight loss. Both T-C and LDL-C elevated more (0.14 vs. -0.21, p = 0.008; 0.31 vs. 0.07, p = 0.015) and TAG and ox-LDL reduced less (-0.33 vs. 0.20, p = 0.033; -3.33 vs. -0.68, p = 0.026) in unaltered weight group compared to weight loss group. The women who gained weight developed higher TAG and ox-LDL/HDL-C ratio as compared to those who lost weight. Postpartum weight retention of 3.4 kg or more is associated with atherogenic lipid profile.

  5. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates.

    Science.gov (United States)

    Lindholm, Marie W; Elmén, Joacim; Fisker, Niels; Hansen, Henrik F; Persson, Robert; Møller, Marianne R; Rosenbohm, Christoph; Ørum, Henrik; Straarup, Ellen M; Koch, Troels

    2012-02-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a therapeutic target for the reduction of low-density lipoprotein cholesterol (LDL-C). PCSK9 increases the degradation of the LDL receptor, resulting in high LDL-C in individuals with high PCSK9 activity. Here, we show that two locked nucleic acid (LNA) antisense oligonucleotides targeting PCSK9 produce sustained reduction of LDL-C in nonhuman primates after a loading dose (20 mg/kg) and four weekly maintenance doses (5 mg/kg). PCSK9 messenger RNA (mRNA) and serum PCSK9 protein were reduced by 85% which resulted in a 50% reduction in circulating LDL-C. Serum total cholesterol (TC) levels were reduced to the same extent as LDL-C with no reduction in high-density lipoprotein levels, demonstrating a specific pharmacological effect on LDL-C. The reduction in hepatic PCSK9 mRNA correlated with liver LNA oligonucleotide content. This verified that anti-PCSK9 LNA oligonucleotides regulated LDL-C through an antisense mechanism. The compounds were well tolerated with no observed effects on toxicological parameters (liver and kidney histology, alanine aminotransferase, aspartate aminotransferase, urea, and creatinine). The pharmacologic evidence and initial safety profile of the compounds used in this study indicate that LNA antisense oligonucleotides targeting PCSK9 provide a viable therapeutic strategy and are potential complements to statins in managing high LDL-C.

  6. Sustained postprandial decrease in plasma levels of LDL cholesterol in patients with type-2 diabetes mellitus

    DEFF Research Database (Denmark)

    Lund, S.S.; Petersen, Martin; Frandsen, M.

    2008-01-01

    Objective. Low density lipoprotein cholesterol (LDL-C) is an independent and modifiable risk factor for development of cardiovascular disease (CVD). Postprandial lipid metabolism has been linked to CVD, but little is known about the postprandial LDL-C profile in patients with type-2 diabetes (T2DM......). We aimed to study the postprandial levels of LDL-C in T2DM patients. Material and methods. After an overnight fast, 74 T2DM patients, mean age approximately 60 years, were served a standard fat-rich meal of 3,515 kJ containing 54 % fat, 13 % protein and 33 % carbohydrates. Only drinking water...... inhibitors; lipoproteins; low density lipoprotein cholesterol (LDL-C); postprandial period; statins; ultracentrifugation...

  7. Effect of sesamin on serum cholesterol and triglycerides levels in LDL receptor-deficient mice

    OpenAIRE

    Peñalvo, José L.; Hopia, Anu; Adlercreutz, Herman

    2006-01-01

    Background Sesamin, a major lignan from sesame seeds has been associated with cholesterol reduction in previous reports, but recent studies suggested differences in the response to sesamin intake depending on the model studied as well as the nature of the sesamin preparation used. Aim The effect of pure sesamin epimer on serum lipids was studied in hypercholesterolemic LDL receptor-knockout mice under cholesterol fed condition. Design Animals were randomly assigned to 4 groups, fed an atherog...

  8. Improvement of HDL- and LDL-cholesterol levels in diabetic subjects by feeding bread containing chitosan.

    Science.gov (United States)

    Ausar, S F; Morcillo, M; León, A E; Ribotta, P D; Masih, R; Vilaro Mainero, M; Amigone, J L; Rubin, G; Lescano, C; Castagna, L F; Beltramo, D M; Diaz, G; Bianco, I D

    2003-01-01

    In this work we evaluated the efficacy and safety of a bread formulation containing chitosan in dyslipidemic type 2 diabetic subjects. For this purpose a total of 18 patients were allowed to incorporate to their habitual diets 120 g/day of bread containing 2% (wt/wt) chitosan (chitosan group, n= 9) or standard bread (control group, n= 9). Before the study and after 12 weeks on the modified diet, the following parameters were evaluated: body weight, plasma cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, and hemoglobin A(1c) (HbA(1c)). Compared with the control group, the patients receiving chitosan-containing bread decreased their mean levels of LDL-cholesterol and significantly increased their mean levels of HDL-cholesterol at the end of the study. There were no significant differences in the body weight, serum triglyceride, and HbA(1c). These results suggest that chitosan incorporated into bread formulations could improve the lipoprotein balance similar to typical biliary salts trappers, increasing the HDL- and lowering the LDL-cholesterol, without changing the triglyceride levels. These results warrant further studies over a longer period of time to evaluate if a persistent improvement in levels of lipoproteins can be attained with this strategy.

  9. HDL cholesterol, LDL receptor activity and response to dietary cholesterol *1 A reply to the letter of Cortese, Miller, Marenah and Lewis [2

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.

    1984-01-01

    Variation in the concentration of cholesterol in blood plasma is partly accounted for by differences in diet, age, sex and genetic constitution. No correlation between plasma low density lipoprotein (LDL) cholesterol concentration and the activity of the LDL receptor in white blood cells could be fo

  10. Continuous Dose-Response Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake 1,2

    NARCIS (Netherlands)

    Demonty, I.; Ras, R.T.; Knaap, van der H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A.

    2009-01-01

    Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)¿lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C¿lowering efficacy of different

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  12. LDL cholesterol in CKD-to treat or not to treat?

    NARCIS (Netherlands)

    Massy, Ziad A.; de Zeeuw, Dick

    2013-01-01

    In the majority of patients with chronic kidney disease (CKD) the total and low-density lipoprotein (LDL) cholesterol are usually normal, with the exception of patients with nephrotic-range proteinuria and in peritoneal dialysis patients. Moreover, epidemiological evidence shows that the link betwee

  13. Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL

    Directory of Open Access Journals (Sweden)

    Juan Toledo

    2016-09-01

    Full Text Available This article supports experimental evidence on the time-dependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in “Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1” Ledda et al. (in press [1].

  14. Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL.

    Science.gov (United States)

    Toledo, Juan; Esteve, Montserrat; Grasa, Mar; Ledda, Angelo; Garda, Horacio; Gulfo, José; Ludovico, Ivo Díaz; Ramella, Nahuel; Gonzalez, Marina

    2016-09-01

    This article supports experimental evidence on the time-dependent effect on gene expression related to inflammation and cholesterol deposition in lipid-loaded cells. The cells employed were human monocytes THP1 line transformed into macrophages by treatment with phorbol esters. Macrophages were treated at different times with oxidized low density lipoprotein (Ox-LDL) and then gene expression was measured. We also include data about the different types of oxidized lipoprotein obtained (low, media or high oxidation) for differential exposure with Cu ions. These data include characterization to lipid and protein peroxidative damage and also quantification of cell viability by exposure to native and modified LDL. The present article complements data published in "Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through 11β-hydroxysteroid dehydrogenase type 1" Ledda et al. (in press) [1].

  15. New CETP inhibitor K-312 reduces PCSK9 expression: a potential effect on LDL cholesterol metabolism.

    Science.gov (United States)

    Miyosawa, Katsutoshi; Watanabe, Yuichiro; Murakami, Kentaro; Murakami, Takeshi; Shibata, Haruki; Iwashita, Masaya; Yamazaki, Hiroyuki; Yamazaki, Koichi; Ohgiya, Tadaaki; Shibuya, Kimiyuki; Mizuno, Ken; Tanabe, Sohei; Singh, Sasha A; Aikawa, Masanori

    2015-07-15

    Despite significant reduction of cardiovascular events by statin treatment, substantial residual risk persists, driving emerging needs for the development of new therapies. We identified a novel cholesteryl ester transfer protein (CETP) inhibitor, K-312, that raises HDL and lowers LDL cholesterol levels in animals. K-312 also suppresses hepatocyte expression of proprotein convertase subtilisin/kexin 9 (PCSK9), a molecule that increases LDL cholesterol. We explored the underlying mechanism for the reduction of PCSK9 expression by K-312. K-312 inhibited in vitro human plasma CETP activity (IC50; 0.06 μM). Administration of K-312 to cholesterol-fed New Zealand White rabbits for 18 wk raised HDL cholesterol, decreased LDL cholesterol, and attenuated aortic atherosclerosis. Our search for additional beneficial characteristics of this compound revealed that K-312 decreases PCSK9 expression in human primary hepatocytes and in the human hepatoma cell line HepG2. siRNA silencing of CETP in HepG2 did not compromise the suppression of PCSK9 by K-312, suggesting a mechanism independent of CETP. In HepG2 cells, K-312 treatment decreased the active forms of sterol regulatory element-binding proteins (SREBP-1 and -2) that regulate promoter activity of PCSK9. Chromatin immunoprecipitation assays demonstrated that K-312 decreased the occupancy of SREBP-1 and SREBP-2 on the sterol regulatory element of the PCSK9 promoter. PCSK9 protein levels decreased by K-312 treatment in the circulating blood of cholesterol-fed rabbits, as determined by two independent mass spectrometry approaches, including the recently developed, highly sensitive parallel reaction monitoring method. New CETP inhibitor K-312 decreases LDL cholesterol and PCSK9 levels, serving as a new therapy for dyslipidemia and cardiovascular disease.

  16. Bioactive oat β-glucan reduces LDL cholesterol in Caucasians and non-Caucasians

    Directory of Open Access Journals (Sweden)

    Wolever Thomas MS

    2011-11-01

    Full Text Available Abstract Background There is increasing global acceptance that viscous soluble fibers lower serum LDL cholesterol (LDL-C, but most evidence for this comes from studies in Caucasians. To see if oat β-glucan lowers LDL-C in Caucasians and non-Caucasians we conducted a post-hoc analysis of the results of a randomized, controlled, double-blind, multi-center clinical trial whose primary aim was to determine if molecular-weight (MW influenced the LDL-C-lowering effect of oat β-glucan. Results Caucasian and non-Caucasian subjects with LDL-C-C ≥ 3.0 and ≤ 5.0 mmol/L (n = 786 screened, n = 400 ineligible, n = 19 refused, n = 367 randomized, n = 345 completed, n = 1 excluded for missing ethnicity were randomly assigned to consume cereal containing wheat-fiber (Control, n = 74:13 Caucasian:non-Caucasian or 3 g high-MW (3H, 2,250,000 g/mol, n = 67:19, 4 g medium-MW (4 M, 850,000 g/mol, n = 50:17, 3 g medium-MW (3M, 530,000 g/mol, n = 54:9 or 4 g low-MW (4 L, 210,000 g/mol, n = 51:12 oat β-glucan daily for 4 weeks. LDL-C after 4 weeks was influenced by baseline LDL-C (p Conclusion We conclude that oat β-glucan reduces LDL-C in both Caucasians and non-Caucasians; there was insufficient power to determine if the magnitude of LDL-C-lowering differed by ethnicity. Trial Registration ClinicalTrials.gov: NCT00981981

  17. LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

    Directory of Open Access Journals (Sweden)

    Anna P Lillis

    Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

  18. A novel posttranscriptional mechanism for dietary cholesterol-mediated suppression of liver LDL receptor expression.

    Science.gov (United States)

    Singh, Amar Bahadur; Kan, Chin Fung Kelvin; Shende, Vikram; Dong, Bin; Liu, Jingwen

    2014-07-01

    It is well-established that over-accumulation of dietary cholesterol in the liver inhibits sterol-regulatory element binding protein (SREBP)-mediated LDL receptor (LDLR) gene transcription leading to a reduced hepatic LDLR mRNA level in hypercholesterolemic animals. However, it is unknown whether elevated cholesterol levels can elicit a cellular response to increase LDLR mRNA turnover to further repress LDLR expression in liver tissue. In the current study, we examined the effect of a high cholesterol diet on the hepatic expression of LDLR mRNA binding proteins in three different animal models and in cultured hepatic cells. Our results demonstrate that high cholesterol feeding specifically elevates the hepatic expression of LDLR mRNA decay promoting factor heterogeneous nuclear ribonucleoprotein (HNRNP)D without affecting expressions of other LDLR mRNA binding proteins in vivo and in vitro. Employing the approach of adenovirus-mediated gene knockdown, we further show that depletion of HNRNPD in the liver results in a marked reduction of serum LDL-cholesterol and a substantial increase in liver LDLR expression in hyperlipidemic mice. Additional studies of gene knockdown in albumin-luciferase-untranslated region (UTR) transgenic mice provide strong evidence supporting the essential role of 3'UTR in HNRNPD-mediated LDLR mRNA degradation in liver tissue. Altogether, this work identifies a novel posttranscriptional regulatory mechanism by which dietary cholesterol inhibits liver LDLR expression via inducing HNRNPD to accelerate LDLR mRNA degradation.

  19. Insoluble carob fiber rich in polyphenols lowers total and LDL cholesterol in hypercholesterolemic sujects.

    Science.gov (United States)

    Ruiz-Roso, Baltasar; Quintela, José C; de la Fuente, Ester; Haya, Javier; Pérez-Olleros, Lourdes

    2010-03-01

    Recently, polyphenols have been found to affect blood lipids in animals in a similar manner as soluble dietary fibre. The aim was to assess whether an insoluble dietary fiber very rich in polyphenols has a beneficial effect on serum lipids in humans. In a double-blind randomized placebo-controlled clinical study with parallel arms, 88 volunteers with hypercholesterolemia were randomly assigned to consume daily either, fiber with insoluble 84% polyphenols 4 g twice a day (n = 43) or placebo (n = 45). Serum total, LDL and HDL cholesterol and triglycerides were assessed at baseline and after 4 weeks. The insoluble polyphenols consumption reduced the total cholesterol by 17.8 +/- 6.1% (p < 0.05), LDL cholesterol by 22.5 +/- 8.9% (p < 0.001), LDL: HDL cholesterol ratio by 26.2 +/- 14.3% (p < 0.001) and triglycerides by 16.3 +/- 23.4% (p < 0.05) at the end of the study compared with baseline. No significant differences were found during the study time in the placebo group for the lipid profile. The consumption of fiber very rich in insoluble polyphenols shows beneficial effects on human blood lipid profile and may be effective in prevention and treatment of hyperlipemia.

  20. Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol

    Science.gov (United States)

    Lange, Leslie A.; Hu, Youna; Zhang, He; Xue, Chenyi; Schmidt, Ellen M.; Tang, Zheng-Zheng; Bizon, Chris; Lange, Ethan M.; Smith, Joshua D.; Turner, Emily H.; Jun, Goo; Kang, Hyun Min; Peloso, Gina; Auer, Paul; Li, Kuo-ping; Flannick, Jason; Zhang, Ji; Fuchsberger, Christian; Gaulton, Kyle; Lindgren, Cecilia; Locke, Adam; Manning, Alisa; Sim, Xueling; Rivas, Manuel A.; Holmen, Oddgeir L.; Gottesman, Omri; Lu, Yingchang; Ruderfer, Douglas; Stahl, Eli A.; Duan, Qing; Li, Yun; Durda, Peter; Jiao, Shuo; Isaacs, Aaron; Hofman, Albert; Bis, Joshua C.; Correa, Adolfo; Griswold, Michael E.; Jakobsdottir, Johanna; Smith, Albert V.; Schreiner, Pamela J.; Feitosa, Mary F.; Zhang, Qunyuan; Huffman, Jennifer E.; Crosby, Jacy; Wassel, Christina L.; Do, Ron; Franceschini, Nora; Martin, Lisa W.; Robinson, Jennifer G.; Assimes, Themistocles L.; Crosslin, David R.; Rosenthal, Elisabeth A.; Tsai, Michael; Rieder, Mark J.; Farlow, Deborah N.; Folsom, Aaron R.; Lumley, Thomas; Fox, Ervin R.; Carlson, Christopher S.; Peters, Ulrike; Jackson, Rebecca D.; van Duijn, Cornelia M.; Uitterlinden, André G.; Levy, Daniel; Rotter, Jerome I.; Taylor, Herman A.; Gudnason, Vilmundur; Siscovick, David S.; Fornage, Myriam; Borecki, Ingrid B.; Hayward, Caroline; Rudan, Igor; Chen, Y. Eugene; Bottinger, Erwin P.; Loos, Ruth J.F.; Sætrom, Pål; Hveem, Kristian; Boehnke, Michael; Groop, Leif; McCarthy, Mark; Meitinger, Thomas; Ballantyne, Christie M.; Gabriel, Stacey B.; O’Donnell, Christopher J.; Post, Wendy S.; North, Kari E.; Reiner, Alexander P.; Boerwinkle, Eric; Psaty, Bruce M.; Altshuler, David; Kathiresan, Sekar; Lin, Dan-Yu; Jarvik, Gail P.; Cupples, L. Adrienne; Kooperberg, Charles; Wilson, James G.; Nickerson, Deborah A.; Abecasis, Goncalo R.; Rich, Stephen S.; Tracy, Russell P.; Willer, Cristen J.; Gabriel, Stacey B.; Altshuler, David M.; Abecasis, Gonçalo R.; Allayee, Hooman; Cresci, Sharon; Daly, Mark J.; de Bakker, Paul I.W.; DePristo, Mark A.; Do, Ron; Donnelly, Peter; Farlow, Deborah N.; Fennell, Tim; Garimella, Kiran; Hazen, Stanley L.; Hu, Youna; Jordan, Daniel M.; Jun, Goo; Kathiresan, Sekar; Kang, Hyun Min; Kiezun, Adam; Lettre, Guillaume; Li, Bingshan; Li, Mingyao; Newton-Cheh, Christopher H.; Padmanabhan, Sandosh; Peloso, Gina; Pulit, Sara; Rader, Daniel J.; Reich, David; Reilly, Muredach P.; Rivas, Manuel A.; Schwartz, Steve; Scott, Laura; Siscovick, David S.; Spertus, John A.; Stitziel, Nathaniel O.; Stoletzki, Nina; Sunyaev, Shamil R.; Voight, Benjamin F.; Willer, Cristen J.; Rich, Stephen S.; Akylbekova, Ermeg; Atwood, Larry D.; Ballantyne, Christie M.; Barbalic, Maja; Barr, R. Graham; Benjamin, Emelia J.; Bis, Joshua; Boerwinkle, Eric; Bowden, Donald W.; Brody, Jennifer; Budoff, Matthew; Burke, Greg; Buxbaum, Sarah; Carr, Jeff; Chen, Donna T.; Chen, Ida Y.; Chen, Wei-Min; Concannon, Pat; Crosby, Jacy; Cupples, L. Adrienne; D’Agostino, Ralph; DeStefano, Anita L.; Dreisbach, Albert; Dupuis, Josée; Durda, J. Peter; Ellis, Jaclyn; Folsom, Aaron R.; Fornage, Myriam; Fox, Caroline S.; Fox, Ervin; Funari, Vincent; Ganesh, Santhi K.; Gardin, Julius; Goff, David; Gordon, Ora; Grody, Wayne; Gross, Myron; Guo, Xiuqing; Hall, Ira M.; Heard-Costa, Nancy L.; Heckbert, Susan R.; Heintz, Nicholas; Herrington, David M.; Hickson, DeMarc; Huang, Jie; Hwang, Shih-Jen; Jacobs, David R.; Jenny, Nancy S.; Johnson, Andrew D.; Johnson, Craig W.; Kawut, Steven; Kronmal, Richard; Kurz, Raluca; Lange, Ethan M.; Lange, Leslie A.; Larson, Martin G.; Lawson, Mark; Lewis, Cora E.; Levy, Daniel; Li, Dalin; Lin, Honghuang; Liu, Chunyu; Liu, Jiankang; Liu, Kiang; Liu, Xiaoming; Liu, Yongmei; Longstreth, William T.; Loria, Cay; Lumley, Thomas; Lunetta, Kathryn; Mackey, Aaron J.; Mackey, Rachel; Manichaikul, Ani; Maxwell, Taylor; McKnight, Barbara; Meigs, James B.; Morrison, Alanna C.; Musani, Solomon K.; Mychaleckyj, Josyf C.; Nettleton, Jennifer A.; North, Kari; O’Donnell, Christopher J.; O’Leary, Daniel; Ong, Frank; Palmas, Walter; Pankow, James S.; Pankratz, Nathan D.; Paul, Shom; Perez, Marco; Person, Sharina D.; Polak, Joseph; Post, Wendy S.; Psaty, Bruce M.; Quinlan, Aaron R.; Raffel, Leslie J.; Ramachandran, Vasan S.; Reiner, Alexander P.; Rice, Kenneth; Rotter, Jerome I.; Sanders, Jill P.; Schreiner, Pamela; Seshadri, Sudha; Shea, Steve; Sidney, Stephen; Silverstein, Kevin; Smith, Nicholas L.; Sotoodehnia, Nona; Srinivasan, Asoke; Taylor, Herman A.; Taylor, Kent; Thomas, Fridtjof; Tracy, Russell P.; Tsai, Michael Y.

    2014-01-01

    Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98th or <2nd percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments. PMID:24507775

  1. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson’s Disease

    OpenAIRE

    Sterling, Nicholas W.; Lichtenstein, Maya; Lee, Eun-Young; Lewis, Mechelle M.; Evans, Alicia; Eslinger, Paul J.; Du, Guangwei; Gao, Xiang; Chen, Honglei; Kong, Lan; Huang, Xuemei

    2016-01-01

    Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson’s disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychologica...

  2. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Freiberg, Jacob J; Nordestgaard, Børge G

    2015-01-01

    BACKGROUND: Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD......, myocardial infarction (MI), and all-cause mortality. METHODS: We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years...... of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died. RESULTS: Compared with participants with nonfasting remnant cholesterol cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2...

  3. Association between LDL-cholesterol lowering genetic variants and risk of type 2 diabetes

    Science.gov (United States)

    Lotta, Luca A.; Sharp, Stephen. J; Burgess, Stephen; Perry, John R. B.; Stewart, Isobel. D; Willems, Sara M.; Luan, Jian’an; Ardanaz, Eva; Arriola, Larraitz; Balkau, Beverley; Boeing, Heiner; Deloukas, Panos; Forouhi, Nita G; Franks, Paul W; Grioni, Sara; Kaaks, Rudolf; Key, Timothy J; Navarro, Carmen; Nilsson, Peter M; Overvad, Kim; Palli, Domenico; Panico, Salvatore; Quirós, Jose-Ramón; Riboli, Elio; Rolandsson, Olov; Sacerdote, Carlotta; Salamanca, Elena C; Slimani, Nadia; Spijkerman, Annemieke MW; Tjonneland, Anne; Tumino, Rosario; van der A, Daphne L; van der Schouw, Yvonne T; McCarthy, Mark I.; Barroso, Inês; O’Rahilly, Stephen; Savage, David. B; Sattar, Naveed; Langenberg, Claudia

    2017-01-01

    Importance Low-density lipoprotein (LDL) cholesterol-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with a higher risk of type 2 diabetes, mimicking the increased incidence of new-onset diabetes associated with statin treatment in randomized clinical trials. It is unknown whether alleles near NPC1L1 are also associated with the risk of type 2 diabetes. Objective To investigate whether LDL-lowering alleles in or near NPC1L1 and other genes encoding current or prospective molecular targets of lipid-lowering therapy (i.e. HMGCR, PCSK9, ABCG5/G8, LDLR) are associated with the risk of type 2 diabetes. Design, Setting and Participants The associations with type 2 diabetes and coronary artery disease of LDL-lowering genetic variants were investigated in meta-analyses of genetic association studies. Meta-analyses included 50,775 individuals with type 2 diabetes and 270,269 controls including three studies and 60,801 individuals with coronary artery disease and 123,504 controls from a published meta-analysis. Data collection took place in Europe and the United States between 1991 and 2016. Exposure LDL-lowering alleles in or near NPC1L1, HMGCR, PCSK9, ABCG5/G8, LDLR. Main Outcomes and Measures Odds ratio of type 2 diabetes and coronary artery disease. Results LDL-lowering genetic variants at NPC1L1 were inversely associated with coronary artery disease (odds ratio for a genetically-predicted reduction of 1 mmol/L in LDL cholesterol, 0.61; 95% confidence interval, 0.42-0.88; p=0.008) and directly associated with type 2 diabetes (2.42, 1.70-3.43; p<0.001). The odds ratio of type 2 diabetes for PCSK9 genetic variants was 1.19 (95% confidence interval, 1.02-1.38, p=0.03). For a given reduction in LDL cholesterol, genetic variants were associated with a similar reduction in coronary artery

  4. Modelling approach to simulate reductions in LDL cholesterol levels after combined intake of statins and phytosterols/-stanols in humans

    Directory of Open Access Journals (Sweden)

    Eussen Simone RBM

    2011-10-01

    Full Text Available Abstract Background To examine the effects on LDL cholesterol of the combined use of statins and phytosterols/-stanols, in vivo studies and clinical trials are necessary. However, for a better interpretation of the experimental data as well as to possibly predict cholesterol levels given a certain dosing regimen of statins and phytosterols/-stanols a more theoretically based approach is helpful. This study aims to construct a mathematical model to simulate reductions in low-density lipoprotein (LDL cholesterol in persons who combine the use of statins with a high intake of phytosterols/-stanols, e.g. by the use of functional foods. Methods and Results The proposed model includes the cholesterol pool size in the liver and serum levels of very low-density lipoprotein (VLDL cholesterol. Both an additional and a multiplicative effect of phytosterol/-stanol intake on LDL cholesterol reduction were predicted from the model. The additional effect relates to the decrease of dietary cholesterol uptake reduction, the multiplicative effect relates to the decrease in enterohepatic recycling efficiency, causing increased cholesterol elimination through bile. From the model, it was demonstrated that a daily intake of 2 g phytosterols/-stanols reduces LDL cholesterol level by about 8% to 9% on top of the reduction resulting from statin use. The additional decrease in LDL cholesterol caused by phytosterol/-stanol use at the recommended level of 2 g/d appeared to be similar or even greater than the decrease achieved by doubling the statin dose. Conclusion We proposed a simplified mathematical model to simulate the reduction in LDL cholesterol after separate and combined intake of statins and functional foods acting on intestinal (reabsorption of cholesterol or bile acids in humans. In future work, this model can be extended to include more complex (regulatory mechanisms.

  5. Rice bran extract containing acylated steryl glucoside fraction decreases elevated blood LDL cholesterol level in obese Japanese men.

    Science.gov (United States)

    Ito, Yukihiko; Nakashima, Yuri; Matsuoka, Sayuri

    2015-01-01

    People who frequently consume whole grains show a lower incidence of arteriosclerotic disease than people who consume primarily refined grains. We examined whether or not rice bran extract containing the acylated steryl glucosides (ASG) fraction decreases blood LDL cholesterol levels in obese Japanese men with high blood levels of LDL cholesterol. The study utilized a randomized, double-blind design. A total of 51 subjects were randomly allocated to either a rice bran extract containing ASG fraction (RB-ASG) group or a placebo group. Subjects in the RB-ASG group received 30-50 mg/day of RB-ASG, and the placebo group took 9 capsules/day for 12 weeks. Before and after intake, height, weight, body fat percentage, systolic and diastolic blood pressure were measured, blood was collected, and visceral fat area, subcutaneous fat area, and abdominal circumference were determined based on umbilical computed tomography. Percentage decreases in blood LDL cholesterol, non-HDL cholesterol, LDL/HDL ratio, abdominal circumference and subcutaneous fat area were significantly better in the RB-ASG group than in the placebo group. These findings suggest that RB-ASG fraction may reduce blood LDL cholesterol levels and the risk of arteriosclerosis in obese Japanese men with high LDL cholesterol levels.

  6. Circulating microRNA-126 in patients with coronary artery disease: correlation with LDL cholesterol

    Directory of Open Access Journals (Sweden)

    Sun Xiao

    2012-08-01

    Full Text Available Abstract Background Coronary artery disease (CAD is a major problem worldwide. Atherosclerosis and thrombosis underlying CAD involve multiple cell types. New and useful diagnostic markers are required. MicroRNAs (miRNAs are a class of noncoding RNAs that posttranscriptionally regulate the gene expressions involved in various cellular processes. Endothelial dysfunction is implicated in early processes of athero-thrombosis. Thus, it was hypothesized that the level of vascular endothelium-enriched miRNAs would be altered in plasma samples of CAD patients. Methods Vascular endothelium-enriched miRNA (miR-126 level was analyzed in plasma from 31 patients with CAD and 36 patients without CAD (qRT-PCR analysis. Results MiR-126 was not significantly down-regulated or up-regulated in CAD patients. Interestingly, the level of miR-126 was significantly decreased in patients with CAD and high low-density lipoprotein (LDL cholesterol level. In contrast, the level of miR-126 was significantly increased when LDL cholesterol was high in patients who had risk factors for CAD but did not have angiographically significant CAD. Conclusion MiR-126 was not significantly down-regulated or up-regulated in CAD patients and was not suitable for discriminating CAD patients from patients without CAD. The oppositely-directed relationship between miR-126 and LDL cholesterol in patients with or without CAD may have significant implications for identifying a potential role of miR-126 in cholesterol metabolism.

  7. Higher Plasma LDL-Cholesterol is Associated with Preserved Executive and Fine Motor Functions in Parkinson's Disease.

    Science.gov (United States)

    Sterling, Nicholas W; Lichtenstein, Maya; Lee, Eun-Young; Lewis, Mechelle M; Evans, Alicia; Eslinger, Paul J; Du, Guangwei; Gao, Xiang; Chen, Honglei; Kong, Lan; Huang, Xuemei

    2016-05-01

    Plasma low density lipoprotein (LDL) cholesterol has been associated both with risk of Parkinson's disease (PD) and with age-related changes in cognitive function. This prospective study examined the relationship between baseline plasma LDL-cholesterol and cognitive changes in PD and matched Controls. Fasting plasma LDL-cholesterol levels were obtained at baseline from 64 non-demented PD subjects (62.7 ± 7.9 y) and 64 Controls (61.3 ± 6.8 y). Subjects underwent comprehensive neuropsychological testing at baseline, 18-, and 36-months. Linear mixed-effects modeling was used to assess the relationships between baseline LDL-cholesterol levels and longitudinal cognitive changes. At baseline, PD patients had lower scores of fine motor (p0.7). The cholesterol - executive set shifting association differed significantly between PDs and Controls (interaction p=0.005), whereas the cholesterol - fine motor association difference did not reach significance (interaction, p=0.104). In summary, higher plasma LDL-cholesterol levels were associated with better executive function and fine motor performance over time in PD, both of which may reflect an effect on nigrostriatal mediation. Confirmation of these results and elucidation of involved mechanisms are warranted, and might lead to feasible therapeutic strategies.

  8. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients: relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    J.A. Krikken; F. Waanders; G.M. Dallinga-Thie; L.D. Dikkeschei; L. Vogt; G.J. Navis; R.P.F. Dullaart

    2009-01-01

    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  9. Antiproteinuric therapy decreases LDL-cholesterol as well as HDL-cholesterol in non-diabetic proteinuric patients : relationships with cholesteryl ester transfer protein mass and adiponectin

    NARCIS (Netherlands)

    Krikken, J. A.; Waanders, F.; Dallinga-Thie, G. M.; Dikkeschei, L. D.; Vogt, L.; Navis, G. J.; Dullaart, R. P. F.

    2009-01-01

    Objective: Dyslipidemia contributes to increased cardiovascular risk in nephrotic syndrome. We questioned whether reduction in proteinuria not only lowers low-density lipoprotein cholesterol (LDL-C), but also high-density lipoprotein cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP)

  10. Effect of Animal and Industrial Trans Fatty Acids on HDL and LDL Cholesterol Levels in Humans - A Quantitative Review

    NARCIS (Netherlands)

    Brouwer, I.A.; Wanders, A.J.; Katan, M.B.

    2010-01-01

    Background: Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid an

  11. Evolocumab (Repatha)--a second PCSK9 inhibitor to lower LDL-Cholesterol.

    Science.gov (United States)

    2015-10-12

    The second FDA-approved PCSK9 inhibitor evolocumab (Repatha) appears to be similar in efficacy and safety to alirocumab (Praluent), but no comparative studies are available. Given by subcutaneous injection every 2 weeks or once monthly, evolocumab can further lower LDL-cholesterol levels by about 60% in patients at high risk for atherosclerotic cardiovascular disease already taking maximal statin therapy. Its effect on cardiovascular outcomes remains to be established. The long-term efficacy and safety of both evolocumab and alirocumab are unknown, and they are expensive.

  12. Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

    DEFF Research Database (Denmark)

    Benn, M; Stene, MC; Nordestgaard, BG;

    2008-01-01

    CONTEXT: We have previously shown that rare mutations in the apolipoprotein B gene (APOB) may result in not only severe hypercholesterolemia and ischemic heart disease but also hypocholesterolemia. Despite this, common single-nucleotide polymorphisms (SNPs) in APOB have not convincingly been...... on cholesterol and apolipoprotein B levels. However, as predicted from the magnitude of the observed LDL cholesterol effects, none of these SNPs predicted risk of ischemic heart disease prospectively in the general population, in a case-control study, or as haplotypes. CONCLUSIONS: Multiple common and rare...... demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN...

  13. Marrubium vulgare extract inhibits human-LDL oxidation and enhances HDL-mediated cholesterol efflux in THP-1 macrophage.

    Science.gov (United States)

    Berrougui, Hicham; Isabelle, Maxim; Cherki, Mounia; Khalil, Abdelouahed

    2006-12-14

    The objective of the present study was to elucidate the beneficial properties of aqueous extracts of Marrubium vulgare (AEM) towards cardiovascular disease by protecting human-LDL against lipid peroxidation and promoting HDL-mediated cholesterol efflux. Human-LDL were oxidised by incubation with CuSO(4) in the presence of increased concentrations of AEM (0-100 microg/ml). LDL lipid peroxidation was evaluated by conjugated diene formation, vitamin E disappearance as well as LDL-electrophoretic mobility. HDL-mediated cholesterol efflux assay was carried out in human THP-1 macrophages. Incubation of LDL with AEM significantly prolonged the lag phase (P=0.014), lowered the progression rate of lipid peroxidation (P=0.004), reduced the disappearance of vitamin E and the electrophoretic mobility in a dose-dependent manner. Also, incubation of HDL with AEM significantly increased HDL-mediated cholesterol efflux from THP-1 macrophages implicating an independent ATP binding cassette A1 (ABCA1) pathways. Our findings suggest that M. vulgare provides a source of natural antioxidants, which inhibit LDL oxidation and enhance reverse cholesterol transport and thus can prevent cardiovascular diseases development. These antioxidant properties increase the anti-atherogenic potential of HDL.

  14. Use of random forest in FTIR analysis of LDL cholesterol and tri-glycerides for hyperlipidemia.

    Science.gov (United States)

    Chen, Hua-Zhou; Tang, Guo-Qiang; Ai, Wu; Xu, Li-Li; Cai, Ken

    2015-01-01

    A quantitative determination method for the diagnosis of hyperlipidemia was developed using Fourier transform infrared (FTIR) spectroscopy. Random forest (RF) was demonstrated as a potential multivariate algorithm for the FTIR analysis of low-density lipoprotein cholesterol (LDL-C) and tri-glycerides (TG) in human serum samples. The informative wavebands for LDL-C and TG were selected based on the Gini importance. The selected wavebands were mainly within the fingerprint region. The RF modeling results were better than those derived using PLS in validation process, because the chance for over-fitting was possibly eliminated in RF algorithm. ARF also demonstrated favorable results in the test process. The prospective model exhibited a higher than 90% true prediction in negative/positive properties for male and female samples. These clinical statistical results indicated the optimization of RF algorithm performed accurately in the FTIR determination of LDL-C and TG. RF is evaluated as a promising tool for diagnosing and controlling hyperlipidemia in populations. The parameter optimization methodology is useful in the improving model accuracy using FTIR spectroscopic technology.

  15. Oriented immobilized anti-LDL antibody carrying poly(hydroxyethyl methacrylate) cryogel for cholesterol removal from human plasma

    Energy Technology Data Exchange (ETDEWEB)

    Bereli, Nilay [Department of Chemistry, Hacettepe University, Beytepe, Ankara (Turkey); Sener, Guelsu [Nanotechnology and Nanomedicine Division, Hacettepe University, Ankara (Turkey); Yavuz, Handan, E-mail: handany@hacettepe.edu.tr [Department of Chemistry, Hacettepe University, Beytepe, Ankara (Turkey); Denizli, Adil [Department of Chemistry, Hacettepe University, Beytepe, Ankara (Turkey)

    2011-07-20

    Low density lipoprotein (LDL) cholesterol is a major ingredient of the plaque that collects in the coronary arteries and causes coronary heart diseases. Among the methods used for the extracorporeal elimination of LDL from intravasal volume, immunoaffinity technique using anti-LDL antibody as a ligand offers superior selectivity and specificity. Proper orientation of the immobilized antibody is the main issue in immunoaffinity techniques. In this study, anti-human {beta}-lipoprotein antibody (anti-LDL antibody) molecules were immobilized and oriented through protein A onto poly(2-hydroxyethyl methacrylate) (PHEMA) cryogel in order to remove LDL from hypercholesterolemic human plasma. PHEMA cryogel was prepared by free radical polymerization initiated with N,N,N',N'-tetramethylene diamine (TEMED). PHEMA cryogel with a swelling degree of 8.89 g H{sub 2}O/g and 67% macro-porosity was characterized by swelling studies, scanning electron microscope (SEM) and blood compatibility tests. All the clotting times were increased when compared with control plasma. The maximum immobilized anti-LDL antibody amount was 63.2 mg/g in the case of random antibody immobilization and 19.6 mg/g in the case of oriented antibody immobilization (protein A loading was 57.0 mg/g). Random and oriented anti-LDL antibody immobilized PHEMA cryogels adsorbed 111 and 129 mg LDL/g cryogel from hypercholesterolemic human plasma, respectively. Up to 80% of the adsorbed LDL was desorbed. The adsorption-desorption cycle was repeated 6 times using the same cryogel. There was no significant loss of LDL adsorption capacity. - Research highlights: {yields} LDL cholesterol is a risk factor in the development of coronary heart diseases. {yields} Antibodies against LDL are used for the selective extracorporeal removal of LDL. {yields} Protein A is used for the oriented immobilization of anti LDL onto PHEMA cryogel. {yields} PHEMA cryogels are biocompatible, exhibit a low pressure drop, lack diffusion

  16. An olive oil-rich diet results in higher concentrations of LDL cholesterol and a higher number of LDL subfraction particles than rapeseed oil and sunflower oil diets.

    Science.gov (United States)

    Pedersen, A; Baumstark, M W; Marckmann, P; Gylling, H; Sandström, B

    2000-12-01

    We investigated the effect of olive oil, rapeseed oil, and sunflower oil on blood lipids and lipoproteins including number and lipid composition of lipoprotein subclasses. Eighteen young, healthy men participated in a double-blinded randomized cross-over study (3-week intervention period) with 50 g of oil per 10 MJ incorporated into a constant diet. Plasma cholesterol, triacylglycerol, apolipoprotein B, and very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) cholesterol concentrations were 10;-20% higher after consumption of the olive oil diet compared with the rapeseed oil and sunflower oil diets [analysis of variance (ANOVA), P sunflower oil diets (ANOVA, P sunflower oil (ANOVA, P sunflower oil had more favorable effects on blood lipids and plasma apolipoproteins as well as on the number and lipid content of LDL subfractions compared with olive oil. Some of the differences may be attributed to differences in the squalene and phytosterol contents of the oils.

  17. PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab.

    Science.gov (United States)

    Dahagam, Chanukya; Goud, Aditya; Abdelqader, Abdelhai; Hendrani, Aditya; Feinstein, Matthew J; Qamar, Arman; Joshi, Parag H; Swiger, Kristopher J; Byrne, Kathleen; Quispe, Renato; Jones, Steven R; Blumenthal, Roger S; Martin, Seth S

    2016-03-01

    Patients with familial hypercholesterolemia or statin intolerance are especially challenging to manage since LDL cholesterol levels often remain considerably elevated despite clinicians' best efforts. With statins regarded as first-line pharmacologic therapy by the current American College of Cardiology/American Heart Association guidelines to reduce LDL cholesterol and cardiovascular risk, there is now a critical need to determine when other agents will play a role beyond maximally tolerated statin therapy and lifestyle changes. In this review, we take a closer look at evolocumab (Repatha(®)), one of the new injectable human monoclonal antibodies to PCSK9 and its efficacy and safety properties from the results of various trials.

  18. A randomized trial and novel SPR technique identifies altered lipoprotein-LDL receptor binding as a mechanism underlying elevated LDL-cholesterol in APOE4s

    Science.gov (United States)

    Calabuig-Navarro, M. V.; Jackson, K. G.; Kemp, C. F.; Leake, D. S.; Walden, C. M.; Lovegrove, J. A.; Minihane, A. M.

    2017-01-01

    At a population level APOE4 carriers (~25% Caucasians) are at higher risk of cardiovascular diseases. The penetrance of genotype is however variable and influenced by dietary fat composition, with the APOE4 allele associated with greater LDL-cholesterol elevation in response to saturated fatty acids (SFA). The etiology of this greater responsiveness is unknown. Here a novel surface plasmon resonance technique (SPR) is developed and used, along with hepatocyte (with the liver being the main organ modulating lipoprotein metabolism and plasma lipid levels) uptake studies to establish the impact of dietary fatty acid composition on, lipoprotein-LDL receptor (LDLR) binding, and hepatocyte uptake, according to APOE genotype status. In men prospectively recruited according to APOE genotype (APOE3/3 common genotype, or APOE3/E4), triglyceride-rich lipoproteins (TRLs) were isolated at fasting and 4–6 h following test meals rich in SFA, unsaturated fat and SFA with fish oil. In APOE4s a greater LDLR binding affinity of postprandial TRL after SFA, and lower LDL binding and hepatocyte internalization, provide mechanisms for the greater LDL-cholesterol raising effect. The SPR technique developed may be used for the future study of the impact of genotype, and physiological and behavioral variables on lipoprotein metabolism. Trial registration number NCT01522482. PMID:28276521

  19. EFFECT OF LOWER TARGETS FOR BLOOD PRESSURE AND LDL CHOLESTEROL ON ATHEROSCLEROSIS IN DIABETES

    Science.gov (United States)

    Howard, Barbara V.; Roman, Mary J.; Fleg, Jerome L.; Galloway, James M.; Henderson, Jeffrey A.; Howard, Wm. James; Lee, Elisa T.; Mete, Mihriye; Poolaw, Bryce; Devereux, Richard B.; Russell, Marie; Silverman, Angela; Stylianou, Mario; Umans, Jason; Wang, Wenyu; Weissman, Neil; Weir, Matthew R.; Wilson, Charlton; Yeh, Fawn; Zhu, Jianhui; Ratner, Robert E.

    2008-01-01

    Context Individuals with diabetes are at greatly increased risk for developing cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested. Objective To compare the progression of subclinical atherosclerotic disease in diabetic adults treated to aggressive targets of low-density lipoprotein cholesterol (LDL-C) ≤ 70 mg/dL and blood pressure (BP) ≤ 115/75 mm Hg (aggressive) versus treatment to standard targets of LDL-C ≤ 100 mg/dL and BP ≤ 130/85 mm Hg (standard). Design Randomized, open label, blinded-to-endpoint 3-year trial in individuals with diabetes conducted April 2003-July 2004. Setting Four clinical centers in southwestern Oklahoma; Phoenix, AZ; northeastern Arizona; and South Dakota. Participants 499 American Indian men and women ≥ age 40 with type 2 diabetes and no prior CVD events. Interventions Participants were randomized to aggressive vs. standard treatment. The same treatment algorithms were followed for both groups. Main Outcome Measures Primary endpoint was a composite of progression of atherosclerosis as measured by common carotid artery intimal medial thickness (IMT) and clinical events. Secondary endpoints included other carotid and cardiac ultrasonographic measures. Results LDL-C and systolic BP (SBP) goals for both groups were reached within 12 months and maintained to 36 months. LDL-C and SBP in the last 12 months averaged 72 and 104 mg/dL and 116 and 129 mm Hg in the aggressive and standard groups, respectively. Regression of IMT (-0.017 vs. 0.041 mm, p < .0001) and arterial mass (-0.14 vs. 1.14 mm2, p < .0001) and greater decrease in left ventricular mass (-2.4 vs. -1.3 g/m2.7, p = .05) were observed in the aggressive group. Clinical CVD events were lower than expected and did not differ between groups Conclusions Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events

  20. Inhibitory effect of Piper betel leaf extracts on copper-mediated LDL oxidation and oxLDL-induced lipid accumulation via inducing reverse cholesterol transport in macrophages.

    Science.gov (United States)

    Ma, Gwo-Chin; Wu, Pei-Fang; Tseng, Hsien-Chun; Chyau, Charng-Cherng; Lu, Hsiu-Chin; Chou, Fen-Pi

    2013-12-15

    Piper betel leaf (PBL) has the biological capabilities of detoxification and can work as an anti-inflammatory agent and an anti-oxidant. In this study, we evaluated the anti-oxidative activity of the extract of Piper betel leaves (PBLs) on the basis of Cu(2+)-mediated oxidation, and its ability to prevent foam cell formation in a model for oxidised low density lipoprotein (oxLDL)-induced lipid accumulation in macrophages. Our data demonstrated that PBLs were able to inhibit LDL oxidation in vitro and are able to reduce the lipid accumulation in macrophages. We showed the underlying mechanisms to be the following: PBLs up-regulated the protein levels of the class A and class B scavenger receptors, the membrane lipid transporter ABCA1, and its upstream regulator Liver X receptor (LXR) in the macrophages exposed to oxLDL. The results suggested that PBLs activated the reverse cholesterol transport mechanism to enhance the metabolism of the oxLDL that could prevent both lipid accumulation and foam cell formation and further minimise the possible damage of vessels caused by the oxLDL.

  1. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on the modification of the authorisation of a health claim related to plant sterol esters and lowering blood LDL-cholesterol; high blood LDL-cholesterol is a risk factor in the development

    DEFF Research Database (Denmark)

    Tetens, Inge

    of a health claim related to plant sterol esters and lowering blood LDL-cholesterol (high blood LDL-cholesterol is a risk factor in the development of (coronary) heart disease), pursuant to Article 14 of Regulation (EC) No 1924/2006. The applicant requested an extension of the conditions of use to powder...... supplements to be diluted in water at a dose of 2 g per day, which would lower blood LDL-cholesterol concentrations by “5.4-8.1 %” after six weeks of daily consumption. Plant sterol esters are sufficiently characterised. Lowering blood LDL-cholesterol concentrations is a beneficial physiological effect...... and elevated blood LDL-cholesterol concentration is a risk factor for coronary heart disease. The target population is subjects who need and want to lower their blood cholesterol. In weighing the evidence, the Panel took into account that only one human intervention study showed a reduction in blood LDL-cholesterol...

  2. and white Swiss chard and maintenance of normal blood LDL-cholesterol concentration pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    (Beta vulgaris L. var. cicla) and white Swiss chard (Beta vulgaris L. var. cicla), is sufficiently characterised. The claimed effect, maintenance of normal blood LDL-cholesterol concentration, is a beneficial physiological effect. No human intervention studies from which conclusions could be drawn...... Swiss chard and white Swiss chard and maintenance of normal blood LDL-cholesterol concentration....

  3. The N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans

    Science.gov (United States)

    Weissglas-Volkov, Daphna; Calkin, Anna C.; Tusie-Luna, Teresa; Sinsheimer, Janet S.; Zelcer, Noam; Riba, Laura; Tino, Ana Maria Vargas; Ordoñez-Sánchez, Maria Luisa; Cruz-Bautista, Ivette; Aguilar-Salinas, Carlos A.; Tontonoz, Peter; Pajukanta, Päivi

    2011-01-01

    Atherosclerotic cardiovascular disease (ASCVD) affects more than 1 in 3 American adults. Hypercholesterolemia is a major treatable risk factor for ASCVD, yet many individuals fail to reach target levels of LDL-cholesterol (LDL-C) through the use of statins and lifestyle changes. The E3 ubiquitin ligase myosin regulatory light chain–interacting protein (MYLIP; also known as IDOL) is a recently identified regulator of the LDL receptor (LDLR) pathway. Genome-wide association studies (GWASs) in populations of mixed European descent have identified noncoding variants in the MYLIP region as being associated with LDL-C levels, but no underlying functional variants were pinpointed. In order to fine-map actual susceptibility variants, we studied a population demographically distinct from the discovery population to ensure a different pattern of linkage disequilibrium. Our analysis revealed that in a Mexican population, the nonsynonymous SNP rs9370867, which encodes the N342S amino acid substitution, is an underlying functional variant that was associated with high total cholesterol and accounted for one of the previous significant GWAS signals. Functional characterization showed that the Asn-encoding allele was associated with more potent LDLR degradation and decreased LDL uptake. Mutagenesis of residue 342 failed to affect intrinsic MYLIP E3 ligase activity, but it was critical for LDLR targeting. Our findings suggest that modulation of MYLIP activity can affect LDL-C levels and that pharmacologic inhibition of MYLIP activity might be a useful strategy in the treatment of dyslipidemia and ASCVD. PMID:21765216

  4. Common and Rare Alleles in Apolipoprotein B Contribute to Plasma Levels of LDL Cholesterol in the General Population

    DEFF Research Database (Denmark)

    Benn, M; Stene, MC; Nordestgaard, BG;

    2008-01-01

    demonstrated to affect low-density lipoprotein (LDL) cholesterol levels. OBJECTIVE: We tested the hypothesis that nonsynonymous SNPs in three important functional domains of APOB and APOB tag SNPs predict levels of LDL cholesterol and apolipoprotein B and risk of ischemic heart disease. DESIGN......: This was a prospective study with 25 yr 100% follow up, The Copenhagen City Heart Study. SETTING: The study was conducted in the Danish general population. PARTICIPANTS: Participants included 9185 women and men aged 20-80+ yr. MAIN OUTCOME MEASURES: Levels of LDL cholesterol and apolipoprotein B and risk of ischemic......Q (0.09), E4154K (0.17), and N4311S (0.21). SNPs were associated with increases (T71I, Ivs181708g>t, T2488Tc>t, R3611) or decreases (Ivs4+171c>a, A591V, Ivs18+379a>c, P2712L, E4154, N4311S) in LDL cholesterol from -4.7 to +8.2% (-0.28 to 0.30 mmol/liter; P

  5. Phytosterol intake and dietary fat reduction are independent and additive in their ability to reduce plasma LDL cholesterol

    Science.gov (United States)

    The plasma LDL-cholesterol-lowering effect of plant sterols (PS) appears to be independent of background diet, but definitive proof is lacking. The effect of background diet on plasma concentrations of PS has not been reported. We determined the effects of manipulating dietary contents of PS and f...

  6. Effect of animal and industrial trans fatty acids on HDL and LDL cholesterol levels in humans--a quantitative review.

    Directory of Open Access Journals (Sweden)

    Ingeborg A Brouwer

    Full Text Available BACKGROUND: Trans fatty acids are produced either by industrial hydrogenation or by biohydrogenation in the rumens of cows and sheep. Industrial trans fatty acids lower HDL cholesterol, raise LDL cholesterol, and increase the risk of coronary heart disease. The effects of conjugated linoleic acid and trans fatty acids from ruminant animals are less clear. We reviewed the literature, estimated the effects trans fatty acids from ruminant sources and of conjugated trans linoleic acid (CLA on blood lipoproteins, and compared these with industrial trans fatty acids. METHODOLOGY/PRINCIPAL FINDINGS: We searched Medline and scanned reference lists for intervention trials that reported effects of industrial trans fatty acids, ruminant trans fatty acids or conjugated linoleic acid on LDL and HDL cholesterol in humans. The 39 studies that met our criteria provided results of 29 treatments with industrial trans fatty acids, 6 with ruminant trans fatty acids and 17 with CLA. Control treatments differed between studies; to enable comparison between studies we recalculated for each study what the effect of trans fatty acids on lipoprotein would be if they isocalorically replaced cis mono unsaturated fatty acids. In linear regression analysis the plasma LDL to HDL cholesterol ratio increased by 0.055 (95%CI 0.044-0.066 for each % of dietary energy from industrial trans fatty acids replacing cis monounsaturated fatty acids The increase in the LDL to HDL ratio for each % of energy was 0.038 (95%CI 0.012-0.065 for ruminant trans fatty acids, and 0.043 (95% CI 0.012-0.074 for conjugated linoleic acid (p = 0.99 for difference between CLA and industrial trans fatty acids; p = 0.37 for ruminant versus industrial trans fatty acids. CONCLUSIONS/SIGNIFICANCE: Published data suggest that all fatty acids with a double bond in the trans configuration raise the ratio of plasma LDL to HDL cholesterol.

  7. Butter increased total and LDL cholesterol compared with olive oil but resulted in higher HDL cholesterol compared with a habitual diet

    DEFF Research Database (Denmark)

    Engel, Sara; Tholstrup, Tine

    2015-01-01

    BACKGROUND: Butter is known to have a cholesterol-raising effect and, therefore, has often been included as a negative control in dietary studies, whereas the effect of moderate butter intake has not been elucidated to our knowledge. OBJECTIVE: We compared the effects of moderate butter intake...... their habitual diets. The study included 47 healthy men and women (mean ± SD total cholesterol: 5.22 ± 0.90 mmol/L) who substituted a part of their habitual diets with 4.5% of energy from butter or refined olive oil. RESULTS: Study subjects were 70% women with a mean age and body mass index (in kg/m(2)) of 40.......4 y and 23.5, respectively. Butter intake increased total cholesterol and LDL cholesterol more than did olive oil intake (P cholesterol compared with the run-in period (P

  8. Low LDL cholesterol and increased risk of Parkinson's disease: prospective results from Honolulu-Asia Aging Study.

    Science.gov (United States)

    Huang, Xuemei; Abbott, Robert D; Petrovitch, Helen; Mailman, Richard B; Ross, G Webster

    2008-05-15

    Low-density lipoprotein cholesterol (LDL-C) levels are suggested to be associated inversely with Parkinson's disease (PD). To test the hypothesis that LDL-C levels may increase PD risk, we studied a prospective cohort of 3,233 men (Honolulu-Asia Aging Study) for whom the LDL-C from fasting lipid profiles was obtained during 1991 to 1993. The cohort was followed longitudinally until 2001 for incident Parkinson's cases. During follow-up, 41 men developed PD (18.4/10,000 person-years). Although the incidence of PD increased with decreasing LDL-C in a dose-dependent manner, the association was only significant for men aged 71 to 75 years. In the latter group, risk of PD declined from 38.5/10,000 person-years in men with LDL-C levels or =140 mg/dl. After adjustment for age, smoking, coffee intake, and other factors, the relative odds of PD for men at the 80th versus the 20th percentile of LDL-C (135 vs. 85 mg/dl) was 0.4 (95% confidence interval: 0.2, 0.9). This prospective study supports the hypothesis that low LDL-C is associated with an increased risk of PD. Although confirmation is required, the underlying mechanisms may be useful in understanding key aspects of PD.

  9. Effects of extracted soy isoflavones alone on blood total and LDL cholesterol: Meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Kyoko Taku

    2008-07-01

    Full Text Available Kyoko Taku1, Keizo Umegaki1, Yoshiko Ishimi2, Shaw Watanabe31Information Center, National Institute of Health and Nutrition, Tokyo, Japan; 2Nutritional Epidemiology Program, National Institute of Health and Nutrition, Tokyo, Japan; 3Nutritional Education Program, National Institute of Health and Nutrition, Tokyo, JapanAbstract: When provided concurrently with soy protein for 1–3 months, soy isoflavones exert synergistic or additive cholesterol-lowering effects. This meta-analysis was performed to evaluate the effects of extracted soy isoflavones alone (not ingested concurrently with soy protein on total and low density lipoprotein (LDL cholesterol. MEDLINE (1966–2007, EMBASE (1966–2007, CENTRAL (1966–2007, ICHUSHI (1983–2008, and CNKI (1979–2007 were searched for randomized placebo-controlled trials published in English, Japanese, and Chinese, describing the changes in lipid profiles in adult humans resulting from ingestion of extracted soy isoflavones for 1–3 months. Reference lists of relevant systematic reviews and meta-analyses were hand-searched. Meta-analysis of 10 and 9 trials with usable information using REVMAN found that an average of 70 mg soy isoflavones/day (27–132 mg, as the aglycone form alone had a nonsignificant effect on total (0.01 mmol/L [95% CI: –0.12, 0.14]; P = 0.86 and LDL (0.03 mmol/L [95% CI: –0.11, 0.16]; P = 0.71 cholesterol in menopausal women, respectively. It is concluded that ingestion of about 70 mg extracted soy isoflavones/day alone for 1–3 months does not improve total and LDL cholesterol levels in normocholesterolemic menopausal women; further studies are needed to verify the effects of extracted soy isoflavones.Keywords: extracted soy isoflavones, lipid, total cholesterol, LDL cholesterol

  10. An antibody against the C-terminal domain of PCSK9 lowers LDL cholesterol levels in vivo.

    Science.gov (United States)

    Schiele, Felix; Park, John; Redemann, Norbert; Luippold, Gerd; Nar, Herbert

    2014-02-20

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with autosomal dominant hypercholesterolemia, a state of elevated levels of LDL (low-density lipoprotein) cholesterol. Autosomal dominant hypercholesterolemia can result in severe implications such as stroke and coronary heart disease. The inhibition of PCSK9 function by therapeutic antibodies that block interaction of PCSK9 with the epidermal growth factor-like repeat A domain of LDL receptor (LDLR) was shown to successfully lower LDL cholesterol levels in clinical studies. Here we present data on the identification, structural and biophysical characterization and in vitro and in vivo pharmacology of a PCSK9 antibody (mAb1). The X-ray structure shows that mAb1 binds the module 1 of the C-terminal domain (CTD) of PCSK9. It blocks access to an area bearing several naturally occurring gain-of-function and loss-of-function mutations. Although the antibody does not inhibit binding of PCSK9 to epidermal growth factor-like repeat A, it partially reverses PCSK9-induced reduction of the LDLR and LDL cholesterol uptake in a cellular assay. mAb1 is also effective in lowering serum levels of LDL cholesterol in cynomolgus monkeys in vivo. Complete loss of PCSK9 is associated with insufficient liver regeneration and increased risk of hepatitis C infections. Blocking of the CTD is sufficient to partially inhibit PCSK9 function. Antibodies binding the CTD of PCSK9 may thus be advantageous in patients that do not tolerate complete inhibition of PCSK9.

  11. A novel posttranscriptional mechanism for dietary cholesterol-mediated suppression of liver LDL receptor expression[S

    Science.gov (United States)

    Singh, Amar Bahadur; Kan, Chin Fung Kelvin; Shende, Vikram; Dong, Bin; Liu, Jingwen

    2014-01-01

    It is well-established that over-accumulation of dietary cholesterol in the liver inhibits sterol-regulatory element binding protein (SREBP)-mediated LDL receptor (LDLR) gene transcription leading to a reduced hepatic LDLR mRNA level in hypercholesterolemic animals. However, it is unknown whether elevated cholesterol levels can elicit a cellular response to increase LDLR mRNA turnover to further repress LDLR expression in liver tissue. In the current study, we examined the effect of a high cholesterol diet on the hepatic expression of LDLR mRNA binding proteins in three different animal models and in cultured hepatic cells. Our results demonstrate that high cholesterol feeding specifically elevates the hepatic expression of LDLR mRNA decay promoting factor heterogeneous nuclear ribonucleoprotein (HNRNP)D without affecting expressions of other LDLR mRNA binding proteins in vivo and in vitro. Employing the approach of adenovirus-mediated gene knockdown, we further show that depletion of HNRNPD in the liver results in a marked reduction of serum LDL-cholesterol and a substantial increase in liver LDLR expression in hyperlipidemic mice. Additional studies of gene knockdown in albumin-luciferase-untranslated region (UTR) transgenic mice provide strong evidence supporting the essential role of 3′UTR in HNRNPD-mediated LDLR mRNA degradation in liver tissue. Altogether, this work identifies a novel posttranscriptional regulatory mechanism by which dietary cholesterol inhibits liver LDLR expression via inducing HNRNPD to accelerate LDLR mRNA degradation. PMID:24792925

  12. Antiatherogenic effect of simvastatin is not due to decrease of LDL cholesterol in ovariectomized golden Syrian hamster.

    Science.gov (United States)

    Pitha, J; Bobková, D; Kovár, J; Havlícková, J; Poledne, R

    2010-01-01

    The changes of the composition of blood lipoproteins caused by menopause could also change the effect of hypolipidemic therapy. Using an experimental model we studied the changes of serum lipids and the effect of immediate or delayed treatment with simvastatin on atherosclerosis after surgical menopause. Female golden Syrian hamster aged 6 months were fed hypercholesterolemic diet during the whole study. Atherosclerotic changes in thoracic and abdominal aortas were assessed by stereomicroscopic method after 12 weeks. Four experimental groups were studied: sham-operated animals (n = 5), ovariectomized animals (n = 9), ovariectomized animals treated for 12 weeks (n = 10), and ovariectomized animals treated 4 weeks after ovariectomy for 8 weeks (n = 9). The dose of simvastatin was 10 mg/kg of body weight. After 12 weeks, ovariectomized animals had tenfold higher concentration of triglycerides in LDL fraction and significantly higher prevalence of atherosclerosis than animals without ovariectomy. Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol. However, it improved proportions of pro- and antiatherogenic serum lipids mainly by the increase of HDL cholesterol. The timing of simvastatin treatment had no significant effect on atherosclerotic changes or lipid parameters. Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy. This effect was not mediated by decrease of LDL cholesterol, but by increase in HDL cholesterol.

  13. Mitotic spindle defects and chromosome mis-segregation induced by LDL/cholesterol-implications for Niemann-Pick C1, Alzheimer's disease, and atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Antoneta Granic

    Full Text Available Elevated low-density lipoprotein (LDL-cholesterol is a risk factor for both Alzheimer's disease (AD and Atherosclerosis (CVD, suggesting a common lipid-sensitive step in their pathogenesis. Previous results show that AD and CVD also share a cell cycle defect: chromosome instability and up to 30% aneuploidy-in neurons and other cells in AD and in smooth muscle cells in atherosclerotic plaques in CVD. Indeed, specific degeneration of aneuploid neurons accounts for 90% of neuronal loss in AD brain, indicating that aneuploidy underlies AD neurodegeneration. Cell/mouse models of AD develop similar aneuploidy through amyloid-beta (Aß inhibition of specific microtubule motors and consequent disruption of mitotic spindles. Here we tested the hypothesis that, like upregulated Aß, elevated LDL/cholesterol and altered intracellular cholesterol homeostasis also causes chromosomal instability. Specifically we found that: 1 high dietary cholesterol induces aneuploidy in mice, satisfying the hypothesis' first prediction, 2 Niemann-Pick C1 patients accumulate aneuploid fibroblasts, neurons, and glia, demonstrating a similar aneugenic effect of intracellular cholesterol accumulation in humans 3 oxidized LDL, LDL, and cholesterol, but not high-density lipoprotein (HDL, induce chromosome mis-segregation and aneuploidy in cultured cells, including neuronal precursors, indicating that LDL/cholesterol directly affects the cell cycle, 4 LDL-induced aneuploidy requires the LDL receptor, but not Aß, showing that LDL works differently than Aß, with the same end result, 5 cholesterol treatment disrupts the structure of the mitotic spindle, providing a cell biological mechanism for its aneugenic activity, and 6 ethanol or calcium chelation attenuates lipoprotein-induced chromosome mis-segregation, providing molecular insights into cholesterol's aneugenic mechanism, specifically through its rigidifying effect on the cell membrane, and potentially explaining why ethanol

  14. Type of dyslipidemia and achievement of the LDL-cholesterol goal in chronic kidney disease patients at the University Hospital

    Directory of Open Access Journals (Sweden)

    Sangsawang T

    2015-11-01

    Full Text Available Tamon Sangsawang, Apiradee SriwijitkamolDivision of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandBackground: Chronic kidney disease (CKD has been defined as a coronary artery disease risk equivalent. Therefore, the current guideline has been recommended for CKD patients to reach and maintain a low-density lipoprotein-cholesterol (LDL-C goal of less than 100 mg/dL. However, the data regarding the achievement of LDL-C goal in these patients is lacking.Objective: This study was conducted to evaluate the types of dyslipidemia affecting patients with CKD stages 3 and 4 and to determine whether these patients achieved LDL-C goal.Methods: We performed a retrospective chart review of patients with CKD stage 3 or 4 and dyslipidemia who were followed-up at Siriraj Hospital between October 2011 and September 2012.Results: In total, 150 patients with CKD stage 3 or 4 and dyslipidemia were recruited. The mean age was 72±10 years, and the body mass index was 25.6±4 kg/m2; 60% had CKD stage 3 with an estimated glomerular filtration rate of 34±12 mL/min/1.73 m2, and 54% had type 2 diabetes. The percentage of patients with hypercholesterolemia was 78%, hypertriglyceridemia 54%, and low high-density lipoprotein-C 36%. Of these, 52% had mixed hyperlipidemia. Statin treatment was prescribed to 87% of the patients, of which only 31.3% achieved the LDL-C goal according to the National Cholesterol Education Program and the European Society of Cardiology/European Atherosclerosis Society recommendations. Patients who did not achieve the LDL-C goal had a higher cholesterol level at diagnosis and higher prevalence of type 2 diabetes and stroke than those who achieved it.Conclusion: Two-thirds of CKD patients with hyperlipidemia had mixed hyperlipidemia. Despite the high frequency of statin treatment, only one-third of patients with CKD achieved the LDL-C goal. Thus, a developmental plan

  15. Effect of LDL cholesterol and treatment with losartan on end-stage renal disease in the RENAAL study

    DEFF Research Database (Denmark)

    Tershakovec, A.M.; Keane, W.F.; Zhang, Z.

    2008-01-01

    of losartan- versus placebo-based antihypertensive therapy in patients with type 2 diabetes and nephropathy. LDL cholesterol lowering was associated with a lower risk of ESRD; however, this seemed to be largely an association with the reduction in albuminuria Udgivelsesdato: 2008/3......Renal pathology and dyslipidemia commonly coexist. Treatments that lower albuminuria/proteinuria may lower lipids, but it is not known whether lipid lowering independent of lessening albuminuria/proteinuria slows progression of kidney disease. We examined the association between LDL cholesterol...... levels and treatment with losartan on end-stage renal disease (ESRD). Lipid levels and albuminuria measurements were obtained at baseline and at year 1 in a post hoc analysis from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, which compared the effects...

  16. Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults.

    LENUS (Irish Health Repository)

    Anderwald, Christian

    2010-08-01

    Insulin resistance (IR) is implicated as an independent risk factor for vascular disease. The aim of this study was to assess the impact of family history (FH) of type 2 diabetes (T2DM) and\\/or cardiovascular disease (CVD) on the associations between IR, low-density-lipoprotein cholesterol (LDL-C) and subclinical atherosclerosis (common and internal carotid artery intima media thickness (IMT)) in healthy European adults.

  17. Consumption of a Diet Rich in Cottonseed Oil (CSO Lowers Total and LDL Cholesterol in Normo-Cholesterolemic Subjects

    Directory of Open Access Journals (Sweden)

    Kathleen E. Davis

    2012-06-01

    Full Text Available Animal data indicates that dietary cottonseed oil (CSO may lower cholesterol; however, the effects of a CSO-rich diet have not been evaluated in humans. Thirty-eight healthy adults (aged 18–40; 12 males, 26 females consumed a CSO rich diet (95 g CSO daily for one week. Anthropometric measurements were obtained, and blood was drawn pre- and post-intervention. Serum lipids (total cholesterol (TC, high density lipoprotein (HDL, low density lipoprotein (LDL, triglyceride (TG, and free fatty acids (FFA were assayed. There was no change in weight or waist circumference among participants. There was no change in HDL (Pre: 1.27 ± 0.4 mmol/L; Post: 1.21 ± 0.3 mmol/L or TG (Pre: 0.91 ± 0.6 mmol/L; Post: 1.06 ± 1.0 mmol/L. Total cholesterol and LDL were reduced (TC Pre: 4.39 ± 0.9 mmol/L; Post: 4.16 ± 0.8 mmol/L; LDL Pre: 2.70 ± 0.8 mmol/L; Post: 2.47 ± 0.6 mmol/L. When data were grouped by sex, total cholesterol was reduced in female participants (Pre: 4.34 ± 0.9 mmol/L; Post: 4.09 ± 0.8 mmol/L. Consumption of a high fat, CSO-rich diet for one week reduced total cholesterol in female participants without reducing HDL.

  18. Good vs. Bad Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Good vs. Bad Cholesterol Updated:Apr 3,2017 Cholesterol can't dissolve ... test . View an animation of cholesterol . LDL (Bad) Cholesterol LDL cholesterol is considered the “bad” cholesterol because ...

  19. Clinical characteristics and evaluation of LDL-cholesterol treatment of the Spanish Familial Hypercholesterolemia Longitudinal Cohort Study (SAFEHEART

    Directory of Open Access Journals (Sweden)

    Piedecausa Mar

    2011-06-01

    Full Text Available Abstract Aim Familial hypercholesterolemia (FH patients are at high risk for premature coronary heart disease (CHD. Despite the use of statins, most patients do not achieve an optimal LDL-cholesterol goal. The aims of this study are to describe baseline characteristics and to evaluate Lipid Lowering Therapy (LLT in FH patients recruited in SAFEHEART. Methods and Results A cross-sectional analysis of cases recruited in the Spanish FH cohort at inclusion was performed. Demographic, lifestyle, medical and therapeutic data were collected by specific surveys. Blood samples for lipid profile and DNA were obtained. Genetic test for FH was performed through DNA-microarray. Data from 1852 subjects (47.5% males over 19 years old were analyzed: 1262 (68.1%, mean age 45.6 years had genetic diagnosis of FH and 590 (31.9%, mean age 41.3 years were non-FH. Cardiovascular disease was present in 14% of FH and in 3.2% of non-FH subjects (P Conclusion Although most of this high risk population is receiving LLT, prevalence of cardiovascular disease and LDL-c levels are still high and far from the optimum LDL-c therapeutic goal. However, LDL-c levels could be reduced by using more intensive LLT such as combined therapy with maximum statin dose and ezetimibe.

  20. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial

    NARCIS (Netherlands)

    P.M. Ridker; E. Danielson; F.A. Fonseca; J. Genest; A.M.,Jr Gotto; J.J. Kastelein; W. Koenig; P. Libby; A.J. Lorenzatti; J.G. Macfadyen; B.G. Nordestgaard; J. Shepherd; J.T. Willerson; R.J. Glynn

    2009-01-01

    Background Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations, and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.8 mmol

  1. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial

    DEFF Research Database (Denmark)

    Ridker, Paul M; Danielson, Eleanor; Fonseca, Francisco Ah;

    2009-01-01

    BACKGROUND: Statins lower high-sensitivity C-reactive protein (hsCRP) and cholesterol concentrations, and hypothesis generating analyses suggest that clinical outcomes improve in patients given statins who achieve hsCRP concentrations less than 2 mg/L in addition to LDL cholesterol less than 1.......8 mmol/L (LDL cholesterol and hsCRP after the start of statin therapy is controversial. We prospectively tested this hypothesis. METHODS: In an analysis of 15 548 initially healthy men and women participating in the JUPITER trial (87% of full cohort), we...... to on-treatment concentrations of LDL cholesterol (>/=1.8 mmol/L or /=2 mg/L or

  2. Carbohydrate restriction and dietary cholesterol modulate the expression of HMG-CoA reductase and the LDL receptor in mononuclear cells from adult men

    Directory of Open Access Journals (Sweden)

    Volek Jeff S

    2007-11-01

    Full Text Available Abstract The liver is responsible for controlling cholesterol homeostasis in the body. HMG-CoA reductase and the LDL receptor (LDL-r are involved in this regulation and are also ubiquitously expressed in all major tissues. We have previously shown in guinea pigs that there is a correlation in gene expression of HMG-CoA reductase and the LDL-r between liver and mononuclear cells. The present study evaluated human mononuclear cells as a surrogate for hepatic expression of these genes. The purpose was to evaluate the effect of dietary carbohydrate restriction with low and high cholesterol content on HMG-CoA reductase and LDL-r mRNA expression in mononuclear cells. All subjects were counseled to consume a carbohydrate restricted diet with 10–15% energy from carbohydrate, 30–35% energy from protein and 55–60% energy from fat. Subjects were randomly assigned to either EGG (640 mg/d additional dietary cholesterol or SUB groups [equivalent amount of egg substitute (0 dietary cholesterol contributions per day] for 12 weeks. At the end of the intervention, there were no changes in plasma total or LDL cholesterol (LDL-C compared to baseline (P > 0.10 or differences in plasma total or LDL-C between groups. The mRNA abundance for HMG-CoA reductase and LDL-r were measured in mononuclear cells using real time PCR. The EGG group showed a significant decrease in HMG-CoA reductase mRNA (1.98 ± 1.26 to 1.32 ± 0.92 arbitrary units P

  3. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition.

    Science.gov (United States)

    He, Jiangping; Zhang, Guangya; Pang, Qi; Yu, Cong; Xiong, Jie; Zhu, Jing; Chen, Fengling

    2017-03-09

    SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy. Silencing the key autophagy initiation gene ATG5, reversed the autophagy-promoting effect of SIRT6 in ox-LDL-treated THP1 cells, as evidenced by an increase in foam cells. Cholesterol efflux assays indicated that SIRT6 overexpression in foam cells promoted cholesterol efflux, increased the levels of ABCA1 and ABCG1, and reduced miR-33 levels. By transfecting miR-33 into cells overexpressing SIRT6, we observed that reduced foam cell formation and autophagy flux induction were largely reversed. These data imply that SIRT6 plays an essential role in protecting against atherosclerosis by reducing foam cell formation through an autophagy-dependent pathway. This article is protected by copyright. All rights reserved.

  4. HDL and LDL cholesterol significantly influence beta-cell function in type 2 diabetes mellitus

    NARCIS (Netherlands)

    Kruit, Janine K; Brunham, Liam R; Verchere, C Bruce; Hayden, Michael R

    2010-01-01

    PURPOSE OF REVIEW: Patients with type 2 diabetes mellitus (T2DM) display significant abnormalities in both LDL and HDL particles. Recent data suggest that these changes in lipoprotein particles could contribute to the pathogenesis of T2DM. In this review, we focus on these abnormalities and discuss

  5. Comparison of NCEP performance specifications for triglycerides, HDL-, and LDL-cholesterol with operating specifications based on NCEP clinical and analytical goals.

    Science.gov (United States)

    Fallest-Strobl, P C; Olafsdottir, E; Wiebe, D A; Westgard, J O

    1997-11-01

    The National Cholesterol Education Program (NCEP) performance specifications for methods that measure triglycerides, HDL-cholesterol, and LDL-cholesterol have been evaluated by deriving operating specifications from the NCEP analytical total error requirements and the clinical requirements for interpretation of the tests. We determined the maximum imprecision and inaccuracy that would be allowable to control routine methods with commonly used single and multirule quality-control procedures having 2 and 4 control measurements per run, and then compared these estimates with the NCEP guidelines. The NCEP imprecision specifications meet the operating imprecision necessary to assure meeting the NCEP clinical quality requirements for triglycerides and HDL-cholesterol but not for LDL-cholesterol. More importantly, the NCEP imprecision specifications are not adequate to assure meeting the NCEP analytical total error requirements for any of these three tests. Our findings indicate that the NCEP recommendations fail to adequately consider the quality-control requirements necessary to detect medically important systematic errors.

  6. The effect of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for CVD risk reduction: a systematic review and meta-analysis of randomised-controlled trials.

    Science.gov (United States)

    Ho, Hoang V T; Sievenpiper, John L; Zurbau, Andreea; Blanco Mejia, Sonia; Jovanovski, Elena; Au-Yeung, Fei; Jenkins, Alexandra L; Vuksan, Vladimir

    2016-10-01

    Oats are a rich source of β-glucan, a viscous, soluble fibre recognised for its cholesterol-lowering properties, and are associated with reduced risk of CVD. Our objective was to conduct a systematic review and meta-analysis of randomised-controlled trials (RCT) investigating the cholesterol-lowering potential of oat β-glucan on LDL-cholesterol, non-HDL-cholesterol and apoB for the risk reduction of CVD. MEDLINE, Embase, CINAHL and Cochrane CENTRAL were searched. We included RCT of ≥3 weeks of follow-up, assessing the effect of diets enriched with oat β-glucan compared with controlled diets on LDL-cholesterol, non-HDL-cholesterol or apoB. Two independent reviewers extracted data and assessed study quality and risk of bias. Data were pooled using the generic inverse-variance method with random effects models and expressed as mean differences with 95 % CI. Heterogeneity was assessed by the Cochran's Q statistic and quantified by the I 2-statistic. In total, fifty-eight trials (n 3974) were included. A median dose of 3·5 g/d of oat β-glucan significantly lowered LDL-cholesterol (-0·19; 95 % CI -0·23, -0·14 mmol/l, PHDL-cholesterol (-0·20; 95 % CI -0·26, -0·15 mmol/l, PLDL-cholesterol (I 2=79 %) and non-HDL-cholesterol (I 2=99 %). Pooled analyses showed that oat β-glucan has a lowering effect on LDL-cholesterol, non-HDL-cholesterol and apoB. Inclusion of oat-containing foods may be a strategy for achieving targets in CVD reduction.

  7. The serum LDL/HDL cholesterol ratio is influenced more favorably by exchanging saturated with unsaturated fat than by reducing saturated fat in the diet of women.

    Science.gov (United States)

    Müller, Hanne; Lindman, Anja S; Brantsaeter, Anne Lise; Pedersen, Jan I

    2003-01-01

    We compared the effects of a high fat diet [38.4% of energy (E%) from fat; HSAFA diet, polyunsaturated/saturated fatty acid (P/S) ratio = 0.14], a low fat diet (19.7 E% from fat; LSAFA diet, P/S = 0.17), both based on coconut oil, and a diet with a high content of mono- and polyunsaturated fatty acids (PUFA; 38.2 E% from fat; HUFA diet, P/S = 1.9) on serum lipoproteins. The 25 women studied consumed each diet for 3-wk periods in a crossover design. The two high fat diets were identical except for the quality of the test fat. The LSAFA diet was identical to the HSAFA diet except that half the fat was replaced by carbohydrates. Serum total cholesterol, LDL cholesterol and apoB concentrations did not differ between the HSAFA and the LSAFA diet periods. Total cholesterol, LDL cholesterol and apoB were lower when women consumed the HUFA diet than when they consumed the other two diets. HDL cholesterol and apoA-I were 15 and 11%, respectively, higher when women consumed the HSAFA diet than when they consumed the LSAFA diet; HDL cholesterol and apoA-I were lower when women consumed the HUFA diet than when they consumed the HSAFA diet, but not the LSAFA diet. The LDL cholesterol/HDL cholesterol and apoB/apoA-I ratios were higher when women consumed the LSAFA diet than when they consumed the HSAFA diet. The LDL/HDL cholesterol ratio was higher when women consumed either the LSAFA or the HSAFA diet than when they consumed the HUFA diet, whereas apoB/apoA-I was higher when women consumed the LSAFA diet than when they consumed the HUFA diet. Triacylglycerol and VLDL cholesterol were higher when women consumed the LSAFA diet than when they consumed either the HSAFA or the HUFA diet. We conclude that, to influence the LDL/HDL cholesterol ratio, changing the proportions of dietary fatty acids may be more important than restricting the percentage of total or saturated fat energy, at least when derived mainly from lauric and myristic acids, both of which increase HDL cholesterol.

  8. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial

    DEFF Research Database (Denmark)

    Baigent, Colin; Landray, Martin J; Reith, Christina;

    2011-01-01

    Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess...

  9. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection) : a randomised placebo-controlled trial

    NARCIS (Netherlands)

    Baigent, Colin; Landray, Martin J.; Reith, Christina; Emberson, Jonathan; Wheeler, David C.; Tomson, Charles; Wanner, Christoph; Krane, Vera; Cass, Alan; Craig, Jonathan; Neal, Bruce; Jiang, Lixin; Hooi, Lai Seong; Levin, Adeera; Agodoa, Lawrence; Gaziano, Mike; Kasiske, Bertram; Walker, Robert; Massy, Ziad A.; Feldt-Rasmussen, Bo; Krairittichai, Udom; Ophascharoensuk, Vuddidhej; Fellstrom, Bengt; Holdaas, Hallvard; Tesar, Vladimir; Wiecek, Andrzej; Grobbee, Diederick; de Zeeuw, Dick; Gronhagen-Riska, Carola; Dasgupta, Tanaji; Lewis, David; Herrington, William; Mafham, Marion; Majoni, William; Wallendszus, Karl; Grimm, Richard; Pedersen, Terje; Tobert, Jonathan; Armitage, Jane; Baxter, Alex; Bray, Christopher; Chen, Yiping; Chen, Zhengming; Hill, Michael; Knott, Carol; Parish, Sarah; Simpson, David; Sleight, Peter; Young, Alan; Collins, Rory

    2011-01-01

    Background Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to

  10. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial

    DEFF Research Database (Denmark)

    Baigent, Colin; Landray, Martin J; Reith, Christina;

    2011-01-01

    Lowering LDL cholesterol with statin regimens reduces the risk of myocardial infarction, ischaemic stroke, and the need for coronary revascularisation in people without kidney disease, but its effects in people with moderate-to-severe kidney disease are uncertain. The SHARP trial aimed to assess ...

  11. The impact of cardiovascular risk, baseline LDL-cholesterol, treatment dose and adherence on cost-effectiveness of statins in newly diagnosed diabetes patients

    NARCIS (Netherlands)

    De Vries, Dianna; Hak, Eelko; Postma, Maarten J.

    2015-01-01

    Background: Statins have shown to be cost-effective in most diabetes patients. Treatment decisions in patients newly diagnosed with diabetes are primarily based on the cardiovascular risk. The effect of statins is, however, primarily based on the LDL-cholesterol reduction that is achieved, which is

  12. Potential of PCSK9 as a new target for the management of LDL cholesterol

    Directory of Open Access Journals (Sweden)

    Mombelli G

    2015-07-01

    Full Text Available Guiliana Mombelli, Samuela Castelnuovo, Chiara PavanelloCardiovascular Department, Dyslipidemia Center, Azienda Ospedaliera Niguarda Cà Granda, Milan, ItalyAbstract: A large proportion of patients at high risk for cardiovascular disease continue to suffer from cardiovascular events despite current therapies. The need for additional therapies to lower the residual risk has led to research on new pharmacological approaches. The discovery of proteins regulating the activity of the low-density lipoprotein receptor has been a major breakthrough in the development of new cholesterol-lowering drugs. This review describes inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9 as a promising treatment for familial hypercholesterolemia, especially the relatively good short-term safety of PCSK9 inhibitors. In particular, we focus on its additive effect with statins and its advantage as a monotherapy in statin-intolerant patients. The additional low-density lipoprotein cholesterol lowering obtained with PCSK9 inhibition will be able to reduce the additional risk, but its effect on cardiovascular events has to be evaluated in future studies.Keywords: proprotein convertase subtilisin/kexin type 9, PCSK9, additional or replacement therapy to statins, statin intolerance, residual cardiovascular risk

  13. Low-Fat Nondairy Minidrink Containing Plant Stanol Ester Effectively Reduces LDL Cholesterol in Subjects with Mild to Moderate Hypercholesterolemia as Part of a Western Diet

    Directory of Open Access Journals (Sweden)

    Maarit Hallikainen

    2013-01-01

    Full Text Available The cholesterol-lowering efficacy of plant stanol ester (STAEST added to fat- or milk-based products is well documented. However, their efficacy when added to nondairy liquid drinks is less certain. Therefore, we have investigated the cholesterol-lowering efficacy of STAEST added to a soymilk-based minidrink in the hypercholesterolemic subjects. In a randomized, double-blind, placebo-controlled parallel study, the intervention group (n=27 consumed 2.7 g/d of plant stanols as the ester in soymilk-based minidrink (65 mL/d with the control group (n=29 receiving the same drink without added plant stanols once a day with a meal for 4 weeks. Serum total, LDL, and non-HDL cholesterol concentrations were reduced by 8.0, 11.1, and 10.2% compared with controls (P<0.05 for all. Serum plant sterol concentrations and their ratios to cholesterol declined by 12–25% from baseline in the STAEST group while the ratio of campesterol to cholesterol was increased by 10% in the controls (P<0.05 for all. Serum precursors of cholesterol remained unchanged in both groups. In conclusion, STAEST-containing soymilk-based low-fat minidrink consumed once a day with a meal lowered LDL and non-HDL cholesterol concentrations without evoking any side effects in subjects consuming normal Western diet. The clinical trial registration number is NCT01716390.

  14. A Retrospective Cohort Study of the Potency of lipid-lowering therapy and Race-gender Differences in LDL cholesterol control

    Directory of Open Access Journals (Sweden)

    Weiner Mark

    2011-09-01

    Full Text Available Abstract Background Reasons for race and gender differences in controlling elevated low density lipoprotein (LDL cholesterol may be related to variations in prescribed lipid-lowering therapy. We examined the effect of lipid-lowering drug treatment and potency on time until LDL control for black and white women and men with a baseline elevated LDL. Methods We studied 3,484 older hypertensive patients with dyslipidemia in 6 primary care practices over a 4-year timeframe. Potency of lipid-lowering drugs calculated for each treated day and summed to assess total potency for at least 6 and up to 24 months. Cox models of time to LDL control within two years and logistic regression models of control within 6 months by race-gender adjust for: demographics, clinical, health care delivery, primary/specialty care, LDL measurement, and drug potency. Results Time to LDL control decreased as lipid-lowering drug potency increased (P Conclusions Black women and, to a lesser extent, black men and white women were less likely to achieve LDL control than white men after accounting for lipid-lowering drug potency as well as diverse patient and provider factors. Future work should focus on the contributions of medication adherence and response to treatment to these clinically important differences.

  15. Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.

    Directory of Open Access Journals (Sweden)

    Patrick Linsel-Nitschke

    Full Text Available BACKGROUND: Rare mutations of the low-density lipoprotein receptor gene (LDLR cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD. Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. METHODS: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. FINDINGS: Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11% was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI [0.13-0.24] mmol/L, p = 1.5x10(-10. This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76-0.89], p = 2.1x10(-7. Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. CONCLUSION: A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD.

  16. Lifelong Reduction of LDL-Cholesterol Related to a Common Variant in the LDL-Receptor Gene Decreases the Risk of Coronary Artery Disease—A Mendelian Randomisation Study

    Science.gov (United States)

    Linsel-Nitschke, Patrick; Götz, Anika; Erdmann, Jeanette; Braenne, Ingrid; Braund, Peter; Hengstenberg, Christian; Stark, Klaus; Fischer, Marcus; Schreiber, Stefan; El Mokhtari, Nour Eddine; Schaefer, Arne; Schrezenmeier, Jürgen; Rubin, Diana; Hinney, Anke; Reinehr, Thomas; Roth, Christian; Ortlepp, Jan; Hanrath, Peter; Hall, Alistair S.; Mangino, Massimo; Lieb, Wolfgang; Lamina, Claudia; Heid, Iris M.; Doering, Angela; Gieger, Christian; Peters, Annette; Meitinger, Thomas; Wichmann, H.-Erich; König, Inke R.; Ziegler, Andreas; Kronenberg, Florian; Samani, Nilesh J.; Schunkert, Heribert

    2008-01-01

    Background Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD. Methods Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level. Replication of association with LDL-C level was sought for the most significant single nucleotide polymorphism (SNP) within the LDLR gene in three European samples comprising 6 642 adults and 533 children. Association of this SNP with CAD was examined in six case-control studies involving more than 15 000 individuals. Findings Each copy of the minor T allele of SNP rs2228671 within LDLR (frequency 11%) was related to a decrease of LDL-C levels by 0.19 mmol/L (95% confidence interval (CI) [0.13–0.24] mmol/L, p = 1.5×10−10). This association with LDL-C was uniformly found in children, men, and women of all samples studied. In parallel, the T allele of rs2228671 was associated with a significantly lower risk of CAD (Odds Ratio per copy of the T allele: 0.82, 95% CI [0.76–0.89], p = 2.1×10−7). Adjustment for LDL-C levels by logistic regression or Mendelian Randomisation models abolished the significant association between rs2228671 with CAD completely, indicating a functional link between the genetic variant at the LDLR gene locus, change in LDL-C and risk of CAD. Conclusion A common variant at the LDLR gene locus affects LDL-C levels and, thereby, the risk for CAD. PMID:18714375

  17. Effect of curcumin on LDL oxidation in vitro, and lipid peroxidation and antioxidant enzymes in cholesterol fed rabbits.

    Science.gov (United States)

    Mahfouz, Mohamedain M; Zhou, Qi; Kummerow, Fred A

    2011-11-01

    In this study we examined the antioxidant effect of curcumin on lipid oxidation in vitro and in vivo. In vitro, curcumin at 5 microgM concentration completely prevented low-density lipoprotein (LDL) oxidation by CuS0(4), indicating that curcumin is an effective antioxidant in vitro. In vivo, feeding a pure cholesterol (PC)-rich diet to rabbits significantly increased the plasma and liver lipids as well as thiobarbituric acid reactive substances (TBARS) levels. Addition of curcumin to the PC diet did not show any effect on either plasma lipid and TBARS or liver lipids. Liver TBARS tended to decrease but that decrease was not significant. Erythrocyte glutathione peroxidase (GSH-Px) activity was significantly decreased while catalase activity was significantly increased in rabbits fed a PC diet. The addition of curcumin to a PC diet did not show any significant effect on erythrocyte enzyme activities compared to the rabbits fed a PC diet. The liver GSH-Px and catalase activities were significantly decreased in rabbits fed a PC diet, but the addition of curcumin to the PC diet enhanced the liver GSH-Px activity, which became nonsignificantly different from the control group. These results were discussed considering that curcumin may not be well absorbed and it did not reach a level high enough in vivo to overcome the severe hypercholesterolemia and oxidative stress produced by the PC-rich diet.

  18. 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 G; 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...... loss-of-function mutation is associated with lower levels of lipoprotein(a) and with reduced risk of aortic valve stenosis and myocardial infarction. DESIGN: We used two prospective cohort studies of the general population and one patient-based cohort. SETTING: Cohort studies selected at random...... valve stenosis, 0.77 (0.65-0.92) for myocardial infarction, and 0.76 (0.64-0.89) for aortic valve stenosis or myocardial infarction. CONCLUSIONS: PCSK9 R46L carriers have lower levels of lipoprotein(a) and LDL cholesterol as well as reduced risk of aortic valve stenosis and myocardial infarction...

  19. Phenolic-extract from argan oil (Argania spinosa L.) inhibits human low-density lipoprotein (LDL) oxidation and enhances cholesterol efflux from human THP-1 macrophages.

    Science.gov (United States)

    Berrougui, Hicham; Cloutier, Martin; Isabelle, Maxim; Khalil, Abdelouahed

    2006-02-01

    Argan oil is rich in unsaturated fatty acids, tocopherol and phenolic compounds. These protective molecules make further study of its cardiovascular diseases (CVDs) action interesting. Furthermore, no previous study has explored the antioxidant activity of argan oil in comparison with olive oil. The present study was conducted to evaluate the beneficial properties of Virgin argan oil phenolic extracts (VAO-PE) towards CVD by: (A) protecting human (low-density lipoprotein, LDL) against lipid peroxidation and (B) promoting high-density lipoprotein (HDL)-mediated cholesterol efflux. Human LDLs were oxidized by incubation with CuSO(4) in the presence of different concentrations of VAO-PE (0-320mug/ml). LDL lipid peroxidation was evaluated by conjugated diene and MDA formation as well as Vitamin E disappearance. Incubation of LDL with VAO-PE significantly prolonged the lag-phase and lowered the progression rate of lipid peroxidation (Pargan oil provides a source of dietary phenolic antioxidants, which prevent cardiovascular diseases by inhibiting LDL-oxidation and enhancing reverse cholesterol transport. These properties increase the anti-atherogenic potential of HDL.

  20. Activation of the human complement system by cholesterol-rich and pegylated liposomes - Modulation of cholesterol-rich liposome-mediated complement activation by elevated serum LDL and HDL levels

    DEFF Research Database (Denmark)

    Moghimi, S.M.; Hamad, I.; Bunger, R.;

    2006-01-01

    Intravenously infused liposomes may induce cardiopulmonary distress in some human subjects, which is a manifestation of "complement activation-related pseudoallergy." We have now examined liposome-mediated complement activation in human sera with elevated lipoprotein (LDL and HDL) levels, since...... level of S-protein-bound form of the terminal complex (SC5b-9). However, liposome-induced rise of SC5b-9 was significantly suppressed when serum HDL cholesterol levels increased by 30%. Increase of serum LDL to levels similar to that observed in heterozygous familial hypercholesterolemia also suppressed...

  1. Static pressure accelerates ox-LDL-induced cholesterol accumulation via SREBP-1-mediated caveolin-1 downregulation in cultured vascular smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Di-xian, E-mail: luodixian_2@163.com [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); First People' s Hospital of Chenzhou City, Chenzhou 423000, Hunan (China); Xia, Cheng-lai [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Pharmacy, Third Affiliated Hospital Medical College of Guangzhou, Guangzhou 510150, Guangdong (China); Li, Jun-mu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Xiong, Yan [Department of Pharmacology, School of Pharmaceutics, Central South University, Changsha 410083, Hunan (China); Yuan, Hao-yu [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Lusong Center for Disease Control and Prevention, Zhuzhou 412000, Hunan (China); TANG, Zhen-Wang; Zeng, Yixin [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Liao, Duan-fang, E-mail: dfliao66@yahoo.com.cn [Institute of Pharmacy and Pharmacology, College of Science and Technology, University of South China, Hengyang 421001, Hunan (China); Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, Hunan (China)

    2010-12-03

    Research highlights: {yields} Vertical static pressure accelerates ox-LDL-induced cholesterol accumulation in cultured vascular smooth muscle cells. {yields} Static pressure induces SREBP-1 activation. {yields} Static pressure downregulates the expressions of caveolin-1 by activating SREBP-1. {yields} Static pressure also downregulates the transcription of ABCA1 by activating SREBP-1. {yields} Static pressure increases ox-LDL-induced cholesterol accumulation by SREBP-1-mediated caveolin-1 downregulation in vascular smooth muscle cells cultured in vitro. -- Abstract: Objective: To investigate the effect of static pressure on cholesterol accumulation in vascular smooth muscle cells (VSMCs) and its mechanism. Methods: Rat-derived VSMC cell line A10 treated with 50 mg/L ox-LDL and different static pressures (0, 60, 90, 120, 150, 180 mm Hg) in a custom-made pressure incubator for 48 h. Intracellular lipid droplets and lipid levels were assayed by oil red O staining and HPLC; The mRNA levels of caveolin-1 and ABCA1, the protein levels of caveolin-1 SREBP-1 and mature SREBP-1 were respectively detected by RT-PCR or western blot. ALLN, an inhibitor of SREBP metabolism, was used to elevate SREBP-1 protein level in VSMCs treated with static pressure. Results: Static pressures significantly not only increase intracellular lipid droplets in VSMCs, but also elevate cellular lipid content in a pressure-dependent manner. Intracellular free cholesterol (FC), cholesterol ester (CE), total cholesterol (TC) were respectively increased from 60.5 {+-} 2.8 mg/g, 31.8 {+-} 0.7 mg/g, 92.3 {+-} 2.1 mg/g at atmosphere pressure (ATM, 0 mm Hg) to 150.8 {+-} 9.4 mg/g, 235.9 {+-} 3.0 mg/g, 386.7 {+-} 6.4 mg/g at 180 mm Hg. At the same time, static pressures decrease the mRNA and protein levels of caveolin-1, and induce the activation and nuclear translocation of SREBP-1. ALLN increases the protein level of mature SREBP-1 and decreases caveolin-1 expression, so that cellular lipid levels were

  2. High Blood Cholesterol Prevention

    Science.gov (United States)

    ... Million Hearts® WISEWOMAN Program Prevention and Management of High LDL Cholesterol: What You Can Do Recommend on ... like eating a healthy diet, can help prevent high cholesterol. High low-density lipoprotein (LDL) cholesterol increases ...

  3. LDL-C直接测定法与计算法的比较分析%Analysis Comparing of Calculateds and Direct LDL Cholesterol Determination with Method

    Institute of Scientific and Technical Information of China (English)

    叶桂云; 张忠源; 胡望平; 池细俤; 叶健频; 林坚

    2009-01-01

    目的 寻找及评价更合适的低密度脂蛋白胆目醇(LDL-C)直接测定法或计算法.方法 分析295例血清脂质结果.用直接法测定LDL-C和五种计算法比较.结果 比较295例血清脂质分析,以Delong法与RANDOX直接测定法的LDL-C结果最接近(P>0.05),差异无统计学意义.三酰甘油(TG)分组,当TG≤4.52 mmol/L时,直接测定法较Delong法、Friedewald法高(P4.52mmol/L时,多数计算法随TG增高而降低,但Delong法较稳定,比直接测定法高(P4.52 mmol/L时,Delong法比其它方法结果稳定.Delong法比Friedewald法更适用于临床.

  4. 急性冠脉综合征肥胖及非肥胖患者血清LDL-C/HDL-C比值与冠状动脉病变严重程度的相关性%Correlation between LDL cholesterol/HDL cholesterol ratio and severity of coronary disease in obese and non-obese patients with acute coronary syndrome

    Institute of Scientific and Technical Information of China (English)

    宋艳; 王亚萍; 索萌; 卢群; 田刚

    2013-01-01

    Objective To investigate the correlation between low-density lipoprotein cholesterol (LDL-C)/ high-density lipoprotein cholesterol (HDL-C) ratio and severity of coronary disease in obese and non-obese patients with acute coronary syndrome (ACS). Methods Totally 394 patients with ACS were divided into two groups: obesity with ACS [n = 78, BMI≥28 kg/m2 or WHR>0.9 (male) or >0.85 (female)] and non-obesity with ACS (n = 316). Another 101 healthy individuals served as controls. According to results of coronary angiography. Gensini scores were calculated to quantize the severity of coronary arterial stenosis, and blood lipid indices were determined. Gensini scores and blood lipid indices were compared between the first two groups, and linear correlation analysis was made of Gensini scores and blood lipid indices. Results LDL-C/HDL-C ratio was positively correlated with Gensini scores in obese patients with ACS. Gensini scores, total cholesterol (TC) and ApoB were significantly higher in high LDL-C/HDL-C value sub-group than in low LDL-C/HDL-C value sub-group (P0.05). Conclusion Gensini score in obese patients with ACS is significantly correlated with LDL-C/HDL-C ratio. LDL-C/HDL-C ratio may be a better index to estimate the severity of coronary lesion than LDL-C.%目的 探讨急性冠脉综合征(ACS)肥胖及非肥胖患者血清低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)比值与冠状动脉病变严重程度的相关性.方法 收集ACS患者394例,以BMI≥28.0 kg/m2,或WHR男性>0.9,女性>0.85为肥胖标准,分为ACS肥胖组(n=78)和ACS非肥胖组(n=316),体检健康者作为对照组(n=101).根据1984年美国心脏病协会规定的冠脉血管图像分段评价标准和Gensini积分系统对每支血管狭窄程度进行定量分析.比较ACS肥胖组和非肥胖组肥胖指标、血脂指标及Gensini积分水平变化,相关性分析肥胖组Gensini积分与各指标的相关性.结果 ACS肥胖患者LDL-C/HDL-C比值

  5. JTT-130, a microsomal triglyceride transfer protein (MTP inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

    Directory of Open Access Journals (Sweden)

    Shrestha Sudeep

    2005-09-01

    Full Text Available Abstract Background Microsomal transfer protein inhibitors (MTPi have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG. However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control, 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

  6. Interactions between common genetic polymorphisms in ABCG5/G8 and CYP7A1 on LDL cholesterol-lowering response to atorvastatin.

    Science.gov (United States)

    Kajinami, Kouji; Brousseau, Margaret E; Ordovas, Jose M; Schaefer, Ernst J

    2004-08-01

    Cholesterol excretion by ATP binding cassette transporters G5 and G8 (ABCG5/G8) and bile acid biosynthesis by cholesterol 7alpha-hydroxylase (CYP7A1) are major pathways for the removal of cholesterol into bile. To investigate the interactions between common polymorphisms in ABCG5/G8 and CYP7A1 and statin response, we examined the relationships between five non-synonymous polymorphisms in ABCG5/G8 (Q604E, D19H, Y54C, T400K, and A632V) and a promoter variant in CYP7A1 (A-204C) in 337 hypercholesterolemic patients treated with atorvastatin 10mg. The ABCG8 H19 allele was significantly associated with a greater LDL cholesterol reduction relative to the wild type D19 allele (39.6% versus 36.6%, P = 0.043). This difference was enhanced in non-carriers of the CYP7A1 promoter polymorphism (42.7% versus 38.2%, P = 0.048), and was diminished in accordance with the number of CYP7A1 variant alleles (1.8% in heterozygotes and 0.2% in homozygotes). Combination analysis of these polymorphisms explained a greater percentage of LDL cholesterol response variation (8.5% difference across subgroups) than did single polymorphism analysis (4.2% in CYP7A1 and 3.0% in ABCG8 D19H). The other ABCG5/G8 polymorphisms did not show any significant interactions with the CYP7A1 polymorphism. We conclude that the ABCG8 H19 and CYP7A1 C-204 alleles appear to interact in a dose-dependent manner on atorvastatin response.

  7. PENGHAMBATAN OKSIDASI LDL DAN AKUMULASI KOLESTEROL PADA MAKROFAG OLEH EKSTRAK TEMULAWAK (Curcuma xanthorriza Roxb [The Inhibition of Low Density Lipoprotein Oxidation and Cholesterol Accumulation on the Macrophage by Temulawak Extract

    Directory of Open Access Journals (Sweden)

    Aisyah Tri Septiana1

    2006-12-01

    Full Text Available Coronary heart disease is caused among others by atherosclerosis, which is the result of oxidized low density lipoprotein (LDL and cholesterol accumulation on macrophage, and which is inhibited by temulawak (Curcuma xanthorriza Roxb extract. The objective of this study was to find out the kinds and consentration of temulawak extract which could inhibit LDL oxidation, and to find out the effect of temulawak extract on the accumulation of cholesterol on macrophage. Temulawak was extracted by water, ethanol, aceton and dichlorometane. Inhibition of LDL oxidation was found out by measuring the level of malonaldehyde content of oxidized LDL-CuSO4 which was supplemented with water extract, ethanol extract, aceton extract and dichlorometane extract. of temulawak at concentrations of 43 g, 430 g, and 4300 g per ml of LDL. The percentage of malonaldehyde reduction due to supplementation with water extract, ethanol extract, acetone extract and dichloromethane extract was 44.27; 47.68; 51.83 and 61.2 respectively. The inhibition of LDL oxidation by temulawak extract depends on its concentration. The percentage of malonaldehyde reduction due to supplementation with temulawak extract of 43 µg, 430 µg, and 4300 µg per ml of LDL was 43.63; 56.72; and 53.89.. Concentration of temulawak extract resulting in the highest inhibition of LDL oxidation was 430 µg/ml LDL. Temulawak extract tends to inhibit cholesterol accumulation on macrophage. There is a relationship between the inhibition of cholesterol accumulation on the macrophage and the inhibition of LDL oxidation by temulawak extract

  8. LDL receptor mediated endocytosis of plasma LDL-cholesterol%LDL受体介导的血浆低密度脂蛋白胆固醇的内吞

    Institute of Scientific and Technical Information of China (English)

    范丽娟; 李仲

    2014-01-01

    胆固醇是动物细胞细胞膜的重要组成成分,其做为细胞和环境之间的屏障调节细胞膜的流动性.胆固醇是体内所有的类固醇激素和胆酸合成的前体物质,参与体内代谢.同时胆固醇在神经系统的发育中也起着重要的作用.在血浆中胆固醇以低密度脂蛋白和高密度脂蛋白这两种胆固醇运载血脂蛋白的形式运输.动物细胞通过细胞表面的低密度脂蛋白受体(LDL receptor,LDLR)介导的内吞可以从血液中摄取富含胆固醇的低密度脂蛋白,当细胞表面的LDLR的功能缺陷时,可以导致高胆固醇血症,继而引起动脉粥样硬化、冠心病和中风等严重疾病.本文综述了LDL受体的概述及其通过内吞调节血液中低密度脂蛋白胆固醇水平的作用,并对LDL受体的调节进行了阐述.

  9. High intake of regular-fat cheese compared with reduced-fat cheese does not affect LDL cholesterol or risk markers of the metabolic syndrome

    DEFF Research Database (Denmark)

    Raziani, Farinaz; Tholstrup, Tine; Kristensen, Marlene Dahlwad

    2016-01-01

    circumference did not differ significantly between the 3 diets. CONCLUSION: A high daily intake of regular-fat cheese for 12 wk did not alter LDL cholesterol or MetS risk factors differently than an equal intake of reduced-fat cheese or an isocaloric amount of carbohydrate-rich foods. This trial was registered...... was to compare the effects of regular-fat cheese with an equal amount of reduced-fat cheese and an isocaloric amount of carbohydrate-rich foods on LDL cholesterol and risk factors for the metabolic syndrome (MetS). DESIGN: The study was a 12-wk randomized parallel intervention preceded by a 2-wk run-in period....... A total of 164 subjects with ≥2 MetS risk factors were randomly allocated to 1 of 3 intervention groups: regular-fat cheese (REG), reduced-fat cheese (RED), or a no-cheese, carbohydrate control (CHO) group. Subjects in the REG and RED groups replaced part of their daily habitual diet with 80 g cheese/10...

  10. HDL Cholesterol Test

    Science.gov (United States)

    ... products and services. Advertising & Sponsorship: Policy | Opportunities HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  11. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to monacolin K in SYLVAN BIO red yeast rice and maintenance of normal blood LDL - cholesterol concentrations pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    on the scientific substantiation of a health claim related to monacolin K in SYLVAN BIO red yeast rice and maintenance of normal blood LDL-cholesterol concentrations. The food, monacolin K in SYLVAN BIO red yeast rice, that is the subject of the health claim is sufficiently characterised. The claimed effect......, maintenance of normal blood LDL-cholesterol concentrations, is a beneficial physiological effect. A claim on monacolin K from red yeast rice and maintenance of normal blood LDL-cholesterol concentrations has already been assessed with a favourable outcome at daily intakes of 10 mg monacolin K from any red...... on blood LDL-cholesterol concentrations. © European Food Safety Authority, 2013...

  12. Cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) and cholesterol uptake via the LDL receptor influences cholesterol-induced impairment of beta cell function in mice

    NARCIS (Netherlands)

    Kruit, J. K.; Kremer, P. H. C.; Dai, L.; Tang, R.; Ruddle, P.; de Haan, W.; Brunham, L. R.; Verchere, C. B.; Hayden, M. R.

    2010-01-01

    Cellular cholesterol accumulation is an emerging mechanism for beta cell dysfunction in type 2 diabetes. Absence of the cholesterol transporter ATP-binding cassette transporter A1 (ABCA1) results in increased islet cholesterol and impaired insulin secretion, indicating that impaired cholesterol effl

  13. Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

    Science.gov (United States)

    Lanuti, Mirko; Talamonti, Emanuela; Maccarrone, Mauro; Chiurchiù, Valerio

    2015-01-01

    The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC) transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9)-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.

  14. Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Mirko Lanuti

    Full Text Available The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacological activation of GPR55 by its selective agonist O-1602 increased CD36- and SRB-I-mediated lipid accumulation and blocked cholesterol efflux by downregulating ATP-binding cassette (ABC transporters ABCA1 and ABCG1, as well as enhanced cytokine- and pro-metalloprotease-9 (pro-MMP-9-induced proinflammatory responses in foam cells. Treatment with cannabidiol, a selective antagonist of GPR55, counteracted these pro-atherogenic and proinflammatory O-1602-mediated effects. Our data suggest that GPR55 could play deleterious role in ox-LDL-induced foam cells and could be a novel pharmacological target to manage atherosclerosis and other related cardiovascular diseases.

  15. 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.

  16. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

  17. COST-EFFECTIVENESS OF LOWER TARGETS FOR BLOOD PRESSURE AND LDL CHOLESTEROL IN DIABETES: THE STOP ATHEROSCLEROSIS IN NATIVE DIABETICS STUDY (SANDS)

    Science.gov (United States)

    Wilson, Charlton; Huang, Chun-Chih; Shara, Nawar; Howard, Barbara V.; Fleg, Jerome L.; Henderson, Jeffrey A.; Howard, Wm. James; Huentelman, Heather; Lee, Elisa T.; Mete, Mihriye; Russell, Marie; Galloway, James M.; Silverman, Angela; Stylianou, Mario; Umans, Jason; Weir, Matthew R.; Yeh, Fawn; Ratner, Robert E.

    2010-01-01

    Background The Stop Atherosclerosis in Native Diabetics Study (SANDS) reported cardiovascular benefit of aggressive versus standard treatment targets for both low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) in diabetic individuals. Objective In this analysis, we examined within trial cost-effectiveness of aggressive targets of LDL-C ≤70 mg/dL and systolic blood pressure (SBP) ≤115 mmHg vs. standard targets of LDL-C ≤100 mg/dL and SBP ≤130 mmHg. Design Randomized, open label blinded-to-endpoint 3-year trial. Data Sources SANDS clinical trial database, Quality of Wellbeing (QWB) survey, Centers for Medicare and Medicaid Services, Wholesale Drug Prices. Target Population American Indians ≥ age 40 years with type 2 diabetes and no prior cardiovascular events. Time Horizon April 2003-July 2007. Perspective Health payer. Interventions Participants were randomized to aggressive vs. standard groups with treatment algorithms defined for both. Outcome Measures Incremental cost-effectiveness. Results of Base-Case Analysis Compared with the standard group, the aggressive group had slightly lower costs of medical services ($-116), but a 54% higher cost for BP medication ($1,242) and a 116% higher cost for lipid-lowering medication ($2,863), resulting in an increased cost of $3,988 over 3 years. Those in the aggressively treated group gained 0.0480 quality-adjusted life-years (QALY) over the standard group. Using a 3% discount rate for costs and outcomes, the resulting cost per QALY was $82,589. Results of Sensitivity Analysis Using a 25%, 50%, and 75% reduction in drug costs resulted in a cost per QALY of $61,329, $40,070, and $18,810, respectively. Limitations This study was limited by use of a single ethnic group and by its 3-year duration. Conclusions Within this 3-year study, treatment to lower BP and LDL-C below standard targets was not cost-effective due to the cost of the additional medications required to meet the lower targets. With the

  18. A nutraceutical approach (Armolipid Plus) to reduce total and LDL cholesterol in individuals with mild to moderate dyslipidemia: Review of the clinical evidence.

    LENUS (Irish Health Repository)

    Barrios, Vivencio

    2017-02-01

    Compelling evidence supports the effectiveness of the reduction of total and LDL cholesterol (TC and LDL-C) in primarily preventing cardiovascular events, within the framework of life-long prevention programs mainly consisting in lifestyle changes. Pharmacological treatment should be introduced when lifestyle changes, including use of nutraceuticals, have failed. ESC\\/EAS guidelines list a number of nutraceutical compounds and functional foods which have been individually studied in randomized, controlled clinical trials (RCTs). To date only a proprietary formulation of three naturally occurring substances with putative complementary lipid-lowering properties - red yeast rice, policosanol and berberine - combined with folic acid, astaxanthin, and coenzyme Q10 (Armolipid Plus(®)) has been extensively investigated in several RCTs, 7 of which were placebo-controlled, 2 were ezetimibe comparators and 4 were "real life" studies comparing diet and Armolipid Plus to diet alone. The trials included mostly patients with mild to moderate dyslipidemia, treated for 6-48 weeks. The trials also included special populations and patients in whom statins were contraindicated or who could not tolerate them. Armolipid Plus has proved to be able to achieve significant reductions in TC (11-21%) and in LDL-C (15-31%) levels, which is equivalent to expectations from low dose statins. In patients intolerant to statins, who do not achieve their therapeutic target with ezetimibe, Armolipid Plus can achieve a further 10% improvement in TC and LDL-C. The safety and tolerability of Armolipid Plus were excellent, thought likely due to the intentional combination of low doses of its active ingredients: low enough not to be associated with untoward effects, but high enough to exert therapeutic effects in combination with other complementary substances. Consequently, in the event of intolerance to statins, Armolipid Plus offers an effective alternative, which is devoid of the safety risks

  19. A nutraceutical approach (Armolipid Plus) to reduce total and LDL cholesterol in individuals with mild to moderate dyslipidemia: Review of the clinical evidence.

    Science.gov (United States)

    Barrios, Vivencio; Escobar, Carlos; Cicero, Arrigo Francesco Giuseppe; Burke, David; Fasching, Peter; Banach, Maciej; Bruckert, Eric

    2017-02-01

    Compelling evidence supports the effectiveness of the reduction of total and LDL cholesterol (TC and LDL-C) in primarily preventing cardiovascular events, within the framework of life-long prevention programs mainly consisting in lifestyle changes. Pharmacological treatment should be introduced when lifestyle changes, including use of nutraceuticals, have failed. ESC/EAS guidelines list a number of nutraceutical compounds and functional foods which have been individually studied in randomized, controlled clinical trials (RCTs). To date only a proprietary formulation of three naturally occurring substances with putative complementary lipid-lowering properties - red yeast rice, policosanol and berberine - combined with folic acid, astaxanthin, and coenzyme Q10 (Armolipid Plus(®)) has been extensively investigated in several RCTs, 7 of which were placebo-controlled, 2 were ezetimibe comparators and 4 were "real life" studies comparing diet and Armolipid Plus to diet alone. The trials included mostly patients with mild to moderate dyslipidemia, treated for 6-48 weeks. The trials also included special populations and patients in whom statins were contraindicated or who could not tolerate them. Armolipid Plus has proved to be able to achieve significant reductions in TC (11-21%) and in LDL-C (15-31%) levels, which is equivalent to expectations from low dose statins. In patients intolerant to statins, who do not achieve their therapeutic target with ezetimibe, Armolipid Plus can achieve a further 10% improvement in TC and LDL-C. The safety and tolerability of Armolipid Plus were excellent, thought likely due to the intentional combination of low doses of its active ingredients: low enough not to be associated with untoward effects, but high enough to exert therapeutic effects in combination with other complementary substances. Consequently, in the event of intolerance to statins, Armolipid Plus offers an effective alternative, which is devoid of the safety risks

  20. Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women.

    Science.gov (United States)

    Taghizadeh, Mohsen; Hashemi, Teibeh; Shakeri, Hossein; Abedi, Fatemeh; Sabihi, Sima-Sadat; Alizadeh, Sabihe-Alsadat; Asemi, Zatolla

    2014-02-01

    To our knowledge, no reports are available indicating the effects of synbiotic food consumption on blood lipid profiles and biomarkers of oxidative stress among pregnant women. This study was conducted to evaluate the effects of daily consumption of a synbiotic food on blood lipid profiles and biomarkers of oxidative stress in pregnant women. This randomized, double-blind, controlled clinical trial was performed among 52 primigravida pregnant women, aged 18 to 35-year-old at their third trimester. After a 2-week run-in period, subjects were randomly assigned to consume either a synbiotic (n = 26) or control food (n = 26) for 9 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10⁷ CFU) and 0.04 g inulin (HPX)/g as the prebiotic. Patients were asked to consume the synbiotic and control foods two times a day. Biochemical measurements including blood lipid profiles, plasma total antioxidant capacity (TAC) and total glutathione (GSH) were conducted before and after 9 weeks of intervention. Consumption of a synbiotic food for 9 weeks resulted in a significant reduction in serum TAG (P = 0.04), VLDL (P = 0.04) and a significant rise in plasma GSH levels (P = 0.004) compared to the control food. No significant effects of the synbiotic food consumption on serum TC, LDL, HDL and plasma TAC levels (P > 0.05) were observed. Trial registry code: http://www.irct.ir . IRCT201212105623N3.

  1. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol....... Novel genes in LDL metabolism will improve our understanding of mechanisms in LDL metabolism, and may lead to the identification of new drug targets to reduce LDL cholesterol levels.......PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette...

  2. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to a combination of plant sterols and Cholesternorm®mix and reduction of blood LDL-cholesterol concentrations pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    on the scientific substantiation of a health claim related to a combination of plant sterols and Cholesternorm®mix and reduction of blood LDL-cholesterol concentrations. The food which is the subject of the health claim is a combination of plant sterols (free and in esterified form) and Cholesternorm...... to the claimed effect. Reduction of blood LDL-cholesterol concentrations is a beneficial physiological effect. A reduction in blood LDL-cholesterol concentrations reduces the risk of coronary heart disease. The Panel notes that no evidence was provided that plant sterols or constituents other than plant sterols...... in Cholesternorm®mix, which have a role in the claimed effect, could reasonably be expected to have an effect on blood LDL-cholesterol concentrations at the proposed conditions of use. The Panel notes that no human interventions studies were provided from which conclusions could be drawn for the scientific...

  3. Efectos de una intervención educativa sobre los niveles plasmáticos de LDL-colesterol en diabéticos tipo 2 Effects of an educational intervention on plasma levels of LDL cholesterol in type-2 diabetics

    Directory of Open Access Journals (Sweden)

    Carlos Enrique Cabrera-Pivaral

    2001-12-01

    Full Text Available Objetivo. Demostrar las ventajas de una intervención educativa en el control del colesterol de baja densidad (LDL colesterol en el paciente diabético tipo 2. Material y métodos. Se realizó un estudio cuasi experimental con asignación aleatoria de dos grupos de pacientes diabéticos: un grupo de experimento y un grupo control. El grupo de experimento se integró con 25 diabéticos tipo 2 y el control con 24. La intervención educativa-participativa se organizó mediante el proceso de reflexión-acción. Se efectuaron mediciones de los niveles séricos del LDL colesterol basales y mensuales durante los nueve meses de la intervención educativa. Los grupos fueron controlados tomando en cuenta edad y sexo. El análisis estadístico se efectuó con el estadígrafo de Wilcoxon para variables ordinales y grupos relacionados. Resultados. El grupo que recibe la intervención educativa participativa logra un valor promedio de 148.4+/-21.3, en comparación con el grupo control (185+/-24.1 en la medición posterior del colesterol LDL (p£0.05. Conclusiones. La intervención educativa participativa, mediante la promoción de un nuevo estilo de vida en el paciente diabético del tipo 2, contribuye a mejorar el nivel de control metabólico del LDL colesterol. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.htmlObjective. To prove the benefit of an educational intervention for controlling LDL cholesterol levels in LDL cholesterol. Material and Methods. A quasi-experimental study was conducted; diabetic patients were randomly allocated to an experimental and a control group. The experimental group consisted of 25 patients and the control group of 24 patients. The educational intervention was organized through a reflection-action process. LDL cholesterol levels were measured at baseline and monthly during the nine months of the study. The groups were controlled for age and sex. Statistical analysis included

  4. Cholesterol testing and results

    Science.gov (United States)

    Cholesterol test results; LDL test results; VLDL test results; HDL test results; Coronary risk profile results; Hyperlipidemia- ... Some cholesterol is considered good and some is considered bad. Different blood tests can be done to measure each ...

  5. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  6. 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; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    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....

  7. Simvastatin promotes NPC1-mediated free cholesterol efflux from lysosomes through CYP7A1/LXRα signalling pathway in oxLDL-loaded macrophages.

    Science.gov (United States)

    Xu, Xiaoyang; Zhang, Aolin; Halquist, Matthew S; Yuan, Xinxu; Henderson, Scott C; Dewey, William L; Li, Pin-Lan; Li, Ningjun; Zhang, Fan

    2017-02-01

    Statins, 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors, are the first-line medications prescribed for the prevention and treatment of coronary artery diseases. The efficacy of statins has been attributed not only to their systemic cholesterol-lowering actions but also to their pleiotropic effects that are unrelated to cholesterol reduction. These pleiotropic effects have been increasingly recognized as essential in statins therapy. This study was designed to investigate the pleiotropic actions of simvastatin, one of the most commonly prescribed statins, on macrophage cholesterol homeostasis with a focus on lysosomal free cholesterol egression. With simultaneous nile red and filipin staining, analysis of confocal/multi-photon imaging demonstrated that simvastatin markedly attenuated unesterified (free) cholesterol buildup in macrophages loaded with oxidized low-density lipoprotein but had little effect in reducing the sizes of cholesteryl ester-containing lipid droplets; the reduction in free cholesterol was mainly attributed to decreases in lysosome-compartmentalized cholesterol. Functionally, the egression of free cholesterol from lysosomes attenuated pro-inflammatory cytokine secretion. It was determined that the reduction of lysosomal free cholesterol buildup by simvastatin was due to the up-regulation of Niemann-Pick C1 (NPC1), a lysosomal residing cholesterol transporter. Moreover, the enhanced enzymatic production of 7-hydroxycholesterol by cytochrome P450 7A1 and the subsequent activation of liver X receptor α underscored the up-regulation of NPC1. These findings reveal a novel pleiotropic effect of simvastatin in affecting lysosomal cholesterol efflux in macrophages and the associated significance in the treatment of atherosclerosis.

  8. LDL-C边缘升高患者血清ONOO-、脂联素及TNF-α的变化%Adiponectin and tumor necrosis factor α in patients with borderline high low density lipoprotein cholesterol

    Institute of Scientific and Technical Information of China (English)

    丁铭格; 李榕; 王晓明

    2012-01-01

    目的:观察LDL-C边缘升高患者血清过氧亚硝酸阴离子(ONOO-)、脂联素、肿瘤坏死因子-α(TNF-α)水平的变化及意义.方法:选取LDL-C边缘升高患者50例和健康对照者40例,分别采用酶联免疫吸附法和放射免疫法测定血清ONOO-生成的标记物硝基酪氨酸(NT)、脂联素及TNF-α水平.结果:①与对照组比较,LDL-C边缘升高组血浆NT水平[(14.63±4.93)μmol/L∶(24.78±2.21)μmol/L,P<0.01]与脂联素水平[(5.17±2.36)μg/L∶(7.25±3.19)μg/L,P<0.01]增高,而TNF-α水平降低[(101.8±15.66) μg/L∶(50.37±16.31)μg/L,P<0.01].②LDL-C边缘升高组血清LDL-C水平与脂联素水平(r=0.848 5,P<0.01)及NT水平(r=0.908 7,P<0.05)呈正相关,但与TNF-α无统计学相关性(P>0.05).血清脂联素水平与TNF-α呈负相关(r=-0.539 4,P<0.01).结论:LDL-C边缘升高患者血清ONOO-和脂联素增多,TNF-α的分泌下降.%Objective:To explore plasma peroxynitrite, adiponectin (APN) and tumor necrosis factor a (TNF-α) level and their correlation in patients with borderline high low density lipoprotein cholesterol (LDL-C) level. Method:Fifty patients with borderline high LDL-C level and forty normal controls were enrolled in this study. Plasma levels of nitrotyrosine (NT), APN and TNF-α were detected by ELISA and RIA respectively. Result:① Compared with control group, NT ([14. 63 ± 4. 93]μmol/L vs. [24. 78 + 2. 21]μmol/L, P<0.01) and APN ([5. 17±2. 36]μg/L vs. [7. 25±3. 19]μg/L, P<0. 01) were significantly increased in patients with borderline high LDL-C level, and TNF-α concentrations ([101. 8±15. 66]μg/L vs. [50. 37 + 16. 3l]μg/L, P<0. 01) were decreased. ②LDL-C was correlated positively with APN (r=0. 848 5, P<0. 01) and NT (r=0. 908 7, P< 0.05). APN was correlated negatively with TNF-α(r= -0.539 4, P<0. 01). Conclusion: Increased NT and APN, decreased TNF-o levels were represented during the early stage of hypercholesterolemia.

  9. Pantethine, a derivative of vitamin B5, favorably alters total, LDL and non-HDL cholesterol in low to moderate cardiovascular risk subjects eligible for statin therapy: a triple-blinded placebo and diet-controlled investigation

    Directory of Open Access Journals (Sweden)

    Evans M

    2014-02-01

    Full Text Available Malkanthi Evans,1 John A Rumberger,2 Isao Azumano,3 Joseph J Napolitano,4 Danielle Citrolo,5 Toshikazu Kamiya5 1KGK Synergize Inc, London, ON, Canada; 2The Princeton Longevity Center, Princeton, NJ, USA; 3Daiichi Fine Chemical Co, Ltd, Toyama, Japan; 4Independent Consultant, Allentown, PA, USA; 5Kyowa Hakko USA, New York, NY, USA Abstract: High serum concentration of low-density lipoprotein cholesterol (LDL-C is a major risk factor for coronary heart disease. The efficacy of pantethine treatment on cardiovascular risk markers was investigated in a randomized, triple-blinded, placebo-controlled study, in a low to moderate cardiovascular disease (CVD risk North American population eligible for statin therapy, using the National Cholesterol Education Program (NCEP guidelines. A total of 32 subjects were randomized to pantethine (600 mg/day from weeks 1 to 8 and 900 mg/day from weeks 9 to16 or placebo. Compared with placebo, the participants on pantethine showed a significant decrease in total cholesterol at 16 weeks (P=0.040 and LDL-C at 8 and 16 weeks (P=0.020 and P=0.006, respectively, and decreasing trends in non-high-density lipoprotein cholesterol at week 8 and week 12 (P=0.102 and P=0.145, respectively that reached significance by week 16 (P=0.042. An 11% decrease in LDL-C from baseline was seen in participants on pantethine, at weeks 4, 8, 12, and 16, while participants on placebo showed a 3% increase at week 16. This decrease was significant between groups at weeks 8 (P=0.027 and 16 (P=0.010. The homocysteine levels for both groups did not change significantly from baseline to week 16. Coenzyme Q10 significantly increased from baseline to week 4 and remained elevated until week 16, in both the pantethine and placebo groups. After 16 weeks, the participants on placebo did not show significant improvement in any CVD risk end points. This study confirms that pantethine lowers cardiovascular risk markers in low to moderate CVD risk participants

  10. Studies on PCSK9 in the regulation of cholesterol metabolism

    OpenAIRE

    Persson, Lena

    2011-01-01

    Elevated levels of plasma cholesterol, mainly in low density lipoproteins (LDL), are a major risk factor for coronary heart disease. The level of plasma LDL cholesterol (LDL-C) is largely dependent on the number of hepatic LDL receptors (LDLRs). Increased number of LDLRs leads to higher uptake of LDL particles and lower concentration of plasma LDL-C. Proprotein convertase subtilisin Kexin Type 9 (PCSK9) is a novel key regulator in cholesterol metabolism. PCSK9 reduces the numbe...

  11. Predictive value of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio on the cardiovascular events in patients undergoing percutaneous coronary intervention%LDL-C/HDL-C比值对经皮冠脉介入术后患者心血管事件的预测价值

    Institute of Scientific and Technical Information of China (English)

    师姗姗; 刘幼文; 金光临; 潘楚梅; 王涓; 曾繁芳

    2013-01-01

    目的 评估低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)比值对经皮冠脉介入(PCI)术后患者心血管事件的预测价值.方法 选择急性冠脉综合征(ACS)并予前降支置入支架的患者119例,依据血浆LDL-C/HDL-C比值将患者分为3组,随访1年,评估三组患者心血管事件发生率,以及各危险因素与心血管事件发生率的关系.结果 ①与LDL-C/HDL-C比值较低的两组相比,比值较高组患者体重指数、女性患者百分率、吸烟人数及糖化血红蛋白、高敏C反应蛋(hs-CRP)、总胆固醇和LDL-C水平均明显升高,而HDL-C水平和他汀类药物使用率则较低(P<0.05).②第1组风险比(HR)1.04,95%可信区间(CI)0.98~1.08,第2组HR 1.16,95%CI 1.08~1.20,第3组HR 1.27,95%CI 1.19~1.36(P<0.05).随着LDL-C/HDL-C比值的升高,PCI术后1年患者心血管事件发生率也逐渐升高(P<0.05).③Cox比例风险回归模型提示,LDL-C/HDL-C比值对PCI术后心血管事件风险的预测价值优于其他危险因素.结论 LDL-C/HDL-C比值对PCI术后患者1年内心血管事件再发具有一定的预测价值.%Objective To investigate the predictive value of LDL-C/HDL-C ratio on the cardiovascular events in patients with PCI treatment. Methods One hundred and nineteen patients defined as acute coronary syndrome treating with stent implantation in anterior descending artery were enrolled. According to the category of LDL-C/HDL-C ratio, patients were assigned into 3 groups and were followed up for one year to evaluate the occurrence of cardiovascular events and the relationship of cardiovascular events with risk factors. Results (1)Compared to the two low categories of LDL-C/HDL-C ratio groups, body mass index, percentage of female, number of smoker, levels of GHBA1C, hs-CRP, total cholesterol and LDL-C were higher, while level of HDL-C and usage of statin were lower (P<0.05). (2)In line with the escalation of LDL-C/HDL-C ratio, the rate of

  12. Evaluation of the performance of seven LDL-cholesterol direct reagents used in homogeneous methods%低密度脂蛋白胆固醇测定匀相法试剂评价

    Institute of Scientific and Technical Information of China (English)

    国汉邦; 李红霞; 赵海舰; 张传宝; 董军; 满永; 王抒; 陈文祥

    2009-01-01

    目的 评价国内市场7种LDL-C匀相法试剂的分析质量.方法 用超速离心-HPLC法作为比对方法,7种LDL-C试剂与Hitachi 7170A组合构成的7种分析系统为待评常规方法.用比对方法和常规方法同时测定40份新鲜人血清,考察常规方法的精密度、偏差和总误差等.结果 7种匀相法试剂均具有良好的精密度(CV<4%).与超速离心-HPLC法相比,旁法B、D、E和F测定的平均偏差和医学决定水平上的偏差均<4%,符合美国国家胆固醇教育计划(NCEP)的要求.方法 C和G存在明显的特异性问题和校准偏差.所有7种方法测定的总误差均未能达到NCEP的要求,方法A、B、D和E测定的总误差达到美国临床实验室改进修正案(CLIA'88)的要求.结论 目前有些LDL-C匀相法试剂的准确性和特异性尚不能满足要求,临床实验室应重视LDL-C试剂的选择和评价.%Objective To evaluate the performance of seven LDL-cholesterol reagents used in the homogeneous methods. Methods Forty fresh sera from patients were respectively analyzed by all of the seven homogeneous methods and an ultracentrifugation-HPLC method,which served as a reference. Each homogeneous method was performed by Hitachi 7170A according to the manufacturers' in-structions. Precision, accuracy, and total errors were evaluated. Results The total CV was < 4% for all methods. The average bias and bias at medical decision points of methods B, D, E, and F were < 4%, which was in accordance with the NCEP performance guideline. Significant calibration bias and non-specificity were found in methods C and G. The total errors of all seven methods failed to meet the NCEP performance guidelines. The total errors of methods A, B, D,and E were within + 30%, which meet the requirements of Clinical Laboratory Amendment,CLIA'88. Conclusions Some homogeneous LDL-C methods had high calibration bias and non-specificity. Clinical laboratories should pay more attention in selecting LDL-cholesterol

  13. The Dynamics of Oxidized LDL during Atherogenesis

    Directory of Open Access Journals (Sweden)

    Hiroyuki Itabe

    2011-01-01

    Full Text Available Accumulating evidence indicates that oxidized low-density lipoprotein (OxLDL is a useful marker for cardiovascular disease. The uptake of OxLDL by scavenger receptors leads to the accumulation of cholesterol within the foam cells of atherosclerotic lesions. OxLDL has many stimulatory effects on vascular cells, and the presence of OxLDL in circulating blood has been established. According to the classical hypothesis, OxLDL accumulates in the atherosclerotic lesions over a long duration, leading to advanced lesions. However, recent studies on time-course changes of OxLDL in vivo raised a possibility that OxLDL can be transferred between the lesions and the circulation. In this paper, the in vivo dynamics of OxLDL are discussed.

  14. Activation of GPR55 Receptors Exacerbates oxLDL-Induced Lipid Accumulation and Inflammatory Responses, while Reducing Cholesterol Efflux from Human Macrophages

    OpenAIRE

    2015-01-01

    The G protein-coupled receptor GPR55 has been proposed as a new cannabinoid receptor associated with bone remodelling, nervous system excitability, vascular homeostasis as well as in several pathophysiological conditions including obesity and cancer. However, its physiological role and underlying mechanism remain unclear. In the present work, we demonstrate for the first time its presence in human macrophages and its increased expression in ox-LDL-induced foam cells. In addition, pharmacologi...

  15. 新型均相酶法检测sd LDL-C试剂盒的性能评价%Performance Evaluation of New Homogeneous Enzymatic Reagent Kit for Measurement of Small Dense LDL CholesterolLIN Wen-tao1,LI Jiang2,SUN Fei3,ZHAO Xing-bo2,Yasuki Ito4,Motoko Ohta4,YAN

    Institute of Scientific and Technical Information of China (English)

    林文涛; 李江; 孙菲; 赵兴波; Yasuki Ito; Motoko Ohta; 鄢盛恺

    2013-01-01

    Objective To evaluate the analytical performance of new homogeneous enzymatic method reagent kit for small dense LDL cholesterol (sd LDL-C) assay hy using automatic chemistry analyzers capahle of accommodating two reagent assays. Methods Based on CSLI EP documents and other literatures,the sensitivity,precision,linear range,and cross-contami-native rate of reagent kit were analyzed. The accuracy of new homogeneous method was evaluated hy comparing with the density gradient ultracentrifugation method (DGUC). Results All kind of precisions and specificity of new homogeneous method were demonstrated to he good. The sensitivity was 0. 048 mmol/L. The total precisions of low value sample and high value sample were 8. 69% and 4. 64%. There was a good relativity hetween the results of homogeneous method and DGUC (Y=l. 065 4X-1. 8354). And the upper range of linear was 2. 634 mmol/L. All these parameters met the requirements of the manual of reagent kit and clinical applications. Conclusion All performances of new homogenous reagent kit were good for sd LDL-C assay. This new homogenous test is a direct method for the measurement of sd LDL-C and could he used in clinical routine laboratories.%目的 评价小而密低密度脂蛋白胆固醇(sd LDL-C)均相酶法检测试剂盒的性能.方法参照CLSI EP文件及其它文献,评估新型sd LDL-C均相酶法液态双试剂检测试剂盒的灵敏度、精密度、线性范围、抗干扰能力和携带污染率,并以密度梯度超速离心法(DUGC)为参比方法,评价新型sd LDL-C均相酶法液态试剂盒的准确度.结果均相法各项精密度及特异度良好,灵敏度可达0.048 mmol/L,低值样本和高值样本的总精密度分别为8.69%和4.64%,测定结果与DUGC法相关性良好(Y=1.065 4X-1.8354),线性范围上限可达2.634 mmol/L,可以抵抗临床中常见的干扰现象,符合试剂说明书的参数和临床应用的要求.结论新型sd LDL-C均相酶法检测试剂盒各项性能良好,是

  16. 新诊断2型糖尿病合并代谢综合征患者血清LDL-C/HDL-C比值的临床研究%LDL cholesterol/HDL cholesterol ratio in newly diagnosed type 2 diabetic patients complicated with metabolic syndrome

    Institute of Scientific and Technical Information of China (English)

    贾珏; 俞淑琴; 叶菁菁; 尹江宁; 王东; 袁国跃

    2014-01-01

    目的 探讨新诊断2型糖尿病(T2DM)合并代谢综合征(MS)患者血清低密度脂蛋白胆固醇(LDL-C)/高密度脂蛋白胆固醇(HDL-C)比值变化及其与各临床指标的相关性.方法 选择新诊断T2DM患者140例,根据是否合并MS分为MS组73例、非MS组67例,另设立正常对照组73例.所有研究对象均行口服葡萄糖耐量试验(OGTT)及胰岛素释放试验,并检测血糖、胰岛素、血脂等相关生化指标,计算各组LDL-C/HDL-C比值.比较各组临床指标及LDL-C/H DL-C比值水平变化,分析LDL-C/HDL-C比值与各指标的相关性.根据LDL-C/HDL-C水平三分位分组,比较各组MS患病率.结果 MS组(3.18±0.85)及非MS组(2.61士0.93)LDL-C/HDL-C均高于对照组(2.26±0.70),且MS组的LDL-C/HDL-C亦高于非MS组,差异有统计学意义(P<0.05).根据LDL-C/HDL-C水平三分位分组,各组MS患病率分别为11.27%、35.21%、56.34%,随着LDL-C/HDL-C水平升高MS患病率升高(P<0.05).相关分析显示,LDL C/HDL-C比值与体质指数(BMI)、腰围(WC)、腰臀比(WHR)、收缩压、舒张压、餐后2h血糖(PPG)、空腹胰岛素(FINS)、餐后2h胰岛素(PSI)、胰岛素抵抗指数(HOMA-IR)、三酰甘油(TG)、血浆总胆固醇(CHOL)、LDL-C呈正相关(P<0.05),与HDL-C呈负相关(P<0.01).以LDL-C/HDL-C为因变量作多元逐步回归分析,有HDL-C、LDL-C、FINS进入方程(P<0.01).结论 T2DM合并MS患者LDL-C/H DL-C的比值升高,且高水平LDL-C/HDL-C比值患者的MS患病率高,LDL-C/HDL-C比值较单纯LDL-C浓度能更好地评估MS发生的危险性,为MS的预防和治疗提供更简便、有效的方案.

  17. Cowpea protein reduces LDL-cholesterol and apolipoprotein B concentrations, but does not improve biomarkers of inflammation or endothelial dysfunction in adults with moderate hypercholesterolemia.

    Science.gov (United States)

    Frota, Karoline de Macedo Gonçalves; dos Santos Filho, Raul Dias; Ribeiro, Valdenir Queiroz; Arêas, José Alfredo Gomes

    2015-04-01

    Introducción: Los riesgos de las enfermedades cardiovasculares, la principal causa de muerte en el mundo, pueden ser reducidos con la dieta. Proteína caupí en hámsters redujo el colesterol total, LDL-colesterol, así como la esteatosis hepática de manera significativa. Objetivo: Este estudio de prueba de concepto fue verificar si el consumo de proteína de frijol mejora el perfil de lípidos y actúa sobre los biomarcadores de inflamación y disfunción endotelial en pacientes con hipercolesterolemia moderada. Métodos: En un diseño aleatorio doble ciego cruzado, 38 sujetos con hipercolesterolemia (colesterol-LDL = 182,5 ± 2,7 mg/dL) consumieron 25 g / día de aislado de proteína de frijol o 25 g / día de caseína (grupo control) durante seis semanas cada uno, y un intervalo de lavado de cuatro semanas Se recogieron muestras de sangre en ayunas al comienzo y al final de cada período de dieta. Los lípidos (colesterol total, LDL-colesterol, triglicéridos, HDL-colesterol) se determinaron por métodos enzimáticos, apolipoproteínas (apoA-I y apoB) por inmunoensayos normalizados, biomarcadores de inflamación (proteína C reactiva) por turbidimetría y los biomarcadores de disfunción endotelial (molecule-1 de adhesión intercelular y de molécula-1 de adhesión celular vascular) por técnicas de ensayo de inmunoabsorción ligados a enzimas. Resultados y discusión: El consumo de proteínas caupí redujo significativamente el colesterol total (12%), el colesterol LDL (18,9%), colesterol no HDL (16%), apoB (14%), y aumentó el colesterol HDL (2,7%). No se observaron diferencias significativas relacionadas con el grupo de tratamiento para cualquiera de los biomarcadores inflamatorios y de disfunción endotelial. Conclusión: Los presentes hallazgos demostraron el efecto favorable del consumo de proteína caupí en lípidos séricos pro-aterogénicas y apoB en sujetos con hipercolesterolemia moderada, de manera similar a lo observado en un trabajo previo con

  18. Understand Your Risk for High Cholesterol

    Science.gov (United States)

    ... Aortic Aneurysm More Understand Your Risk for High Cholesterol Updated:Apr 1,2016 LDL (bad) cholesterol is ... content was last reviewed on 04/21/2014. Cholesterol Guidelines: Putting the pieces together Myth vs. Truth – ...

  19. A COMPARATIVE STUDY TO MEASURE EFFECTIVE REDUCTION IN LDL CHOLESTEROL USING ROSUVASTATIN 10 mg & ATORVASTATIN 20 mg THERAPY IN HYPERLIPIDEMIA PATIENTS IN HARYANA POPULATION

    Directory of Open Access Journals (Sweden)

    Dr Diwanshu Sharma

    2014-02-01

    Full Text Available Atherosclerosis is a killer disease and is a major cause of death throughout the world. Hyperlipidemia is a major cause of atherosclerosis and atherosclerosis-induced conditions, such as coronary heart disease , ischemic cerebrovascular disease and peripheral vascular disease.1Recently World Health Organization (WHO has declared that by 2020, 60% of cardiovascular cases will be of Indian origin2 and from years 2000 to 2020 disability-adjusted life years lost (DALYs from CHD in India shall double in both men and women from 7.7 and 5.5 million, respectively3.The etiology of Cardiovascular diseases (CVD is complex and multifactorial and is influenced by various modifiable ( hyperlipidemia, obesity, hypertension, diabetes, smoking, physical inactivity, diet and non-modifiable(family history, agerisk factors.4A high concentration of lipids i.e. hyperlipidemia and the increase in concentration of low density lipoprotein (LDL-C has been closely linked to pathophysiology of CAD. Statins have now become one of the most widely used therapeutic classes in clinical practice because the cardiovascular benefits of statins that reduce concentrations of LDL-C and inflammatory markers in primary and secondary prevention have already been confirmed in several randomised studies or meta-analysis.

  20. capacity (ID 4305, 4684), maintenance of normal blood LDL-cholesterol concentrations (ID 1494, 4684), contribution to normal spermatogenesis (ID 1822), “energy metabolism” (ID 1821), and increasing L-carnitine concentrations and/or decreasing free fatty acids in blood during pregnancy (ID 1495) pursuant

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to L-carnitine and faster recovery from muscle fatigue after exercise, skeletal muscle tissue repair, increase in endurance capacity, maintenance of normal blood LDL-cholesterol concentrations, contribution to normal spermatogenesis, “energy metabolism”, and increasing L...

  1. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to 3 g/day plant sterols/stanols and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 19 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    of an application to modify the conditions of use of an authorised Article 14 claim related to 1.5 - 3.0 g plant sterols/stanols per day and lowering blood LDL-cholesterol by 7 - 12 % and reduced risk of (coronary) heart disease. The applicant has further requested that the minimum duration to obtain the effect...... be one to two weeks. The applicant provided a published systematic review and meta-analysis that evaluated the comparative efficacy of plant sterols and plant stanols for lowering blood LDL-cholesterol in healthy and hypercholesterolaemic subjects and an unpublished meta-analysis on 27 randomised....../2010 (yellow fat spreads, dairy products, mayonnaise and salad dressings) have a similar efficacy on blood LDL-cholesterol lowering, that plant sterols and stanol esters at a daily intake of 3 g (range 2.6 g to 3.4 g) plant sterols/stanols in matrices approved by Regulation (EC) No 376/2010 lower LDL-cholesterol...

  2. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to rye fibre and changes in bowel function (ID 825), reduction of post-prandial glycaemic responses (ID 826) and maintenance of normal blood LDL-cholesterol

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to rye fibre and changes in bowel function, reduction of post-prandial glycaemic responses and maintenance of normal blood LDL-cholesterol concentrations. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13...

  3. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof

    1992-01-01

    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  4. policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d - α - tocopheryl hydrogen succinate , riboflavin and inositol hexanicotinate in Limicol ® and reduction of blood LDL - cholesterol concentrations pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claim related to the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol......-cholesterol is a risk factor in the development of coronary heart disease. In weighing the evidence, the Panel took into account that, although no evidence was provided for an LDL-cholesterol lowering effect of any of the single food constituents in Limicol® at the proposed conditions of use or as to how...... policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol hexanicotinate in Limicol® and a reduction in blood LDL-cholesterol concentrations. © European Food Safety Authority, 2013...

  5. Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults.

    Science.gov (United States)

    Price, Ruth K; Keaveney, Edel M; Hamill, Lesley L; Wallace, Julie M W; Ward, Mary; Ueland, Per M; McNulty, Helene; Strain, J J; Parker, Michael J; Welch, Robert W

    2010-12-01

    There is strong evidence that whole-grain foods protect against heart disease. Although underlying mechanisms and components are unclear, betaine, found at high levels in wheat aleurone, may play a role. We evaluated the effects of a diet high in wheat aleurone on plasma betaine and related measures. In a parallel, single-blinded intervention study, 79 healthy participants (aged 45-65 y, BMI ≥ 25 kg/m(2)) incorporated either aleurone-rich cereal products (27 g/d aleurone) or control products balanced for fiber and macronutrients into their habitual diets for 4 wk. Fasting blood samples were taken at baseline and postintervention (4 wk) from participants. Compared with the control, the aleurone products provided an additional 279 mg/d betaine and resulted in higher plasma betaine (P aleurone-rich products into the habitual diet for 4 wk significantly increases plasma betaine concentrations and lowers tHcy, which is attributable to enhanced betaine-homocysteine methyltransferase-mediated remethylation of homocysteine. Although this supports a role for betaine in the protective effects of whole grains, concomitant decreases in LDL suggest more than one component or mechanism may be responsible.

  6. High Fat High Cholesterol Diet (Western Diet) Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived Lipopolysaccharide.

    Science.gov (United States)

    Ghosh, Siddhartha S; Righi, Samuel; Krieg, Richard; Kang, Le; Carl, Daniel; Wang, Jing; Massey, H Davis; Sica, Domenic A; Gehr, Todd W B; Ghosh, Shobha

    2015-01-01

    A high fat meal, frequently known as western diet (WD), exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS) leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx) or WD (Nx+WD). The controls were sham operated animals on normal diet (control) and WD (WD). To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin (PM), a known LPS antagonist, and curcumin (CU), a compound known to ameliorate chronic kidney disease (CKD), was given to Nx animals on western diet (Nx+WD+PM and Nx+WD+CU, respectively). Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.

  7. High Fat High Cholesterol Diet (Western Diet Aggravates Atherosclerosis, Hyperglycemia and Renal Failure in Nephrectomized LDL Receptor Knockout Mice: Role of Intestine Derived Lipopolysaccharide.

    Directory of Open Access Journals (Sweden)

    Siddhartha S Ghosh

    Full Text Available A high fat meal, frequently known as western diet (WD, exacerbates atherosclerosis and diabetes. Both these diseases are frequently associated with renal failure. Recent studies have shown that lipopolysaccharide (LPS leaks into the circulation from the intestine in the setting of renal failure and after WD. However, it is not clear how renal function and associated disorders are affected by LPS. This study demonstrates that circulatory LPS exacerbates renal insufficiency, atherosclerosis and glucose intolerance. Renal insufficiency was induced by 2/3 nephrectomy in LDL receptor knockout mice. Nx animals were given normal diet (Nx or WD (Nx+WD. The controls were sham operated animals on normal diet (control and WD (WD. To verify if LPS plays a role in exaggerating renal insufficiency, polymyxin (PM, a known LPS antagonist, and curcumin (CU, a compound known to ameliorate chronic kidney disease (CKD, was given to Nx animals on western diet (Nx+WD+PM and Nx+WD+CU, respectively. Compared to control, all other groups displayed increased circulatory LPS. The Nx+WD cohort had the highest levels of LPS. Nx group had significant renal insufficiency and glucose intolerance but not atherosclerosis. WD had intense atherosclerosis and glucose intolerance but it did not show signs of renal insufficiency. Compared to other groups, Nx+WD had significantly higher cytokine expression, macrophage infiltration in the kidney, renal insufficiency, glucose intolerance and atherosclerosis. PM treatment blunted the expression of cytokines, deterioration of renal function and associated disorders, albeit not to the levels of Nx, and was significantly inferior to CU. PM is a non-absorbable antibiotic with LPS binding properties, hence its beneficial effect can only be due to its effect within the GI tract. We conclude that LPS may not cause renal insufficiency but can exaggerate kidney failure and associated disorders following renal insufficiency.

  8. A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects.

    Science.gov (United States)

    Ross, Alastair B; Bruce, Stephen J; Blondel-Lubrano, Anny; Oguey-Araymon, Sylviane; Beaumont, Maurice; Bourgeois, Alexandre; Nielsen-Moennoz, Corine; Vigo, Mario; Fay, Laurent-Bernard; Kochhar, Sunil; Bibiloni, Rodrigo; Pittet, Anne-Cécile; Emady-Azar, Shahram; Grathwohl, Dominik; Rezzi, Serge

    2011-05-01

    Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.

  9. 血清 LDL-C 水平与老年射血分数降低性心衰患者预后的关系%Prognostic significance of serum low - density lipoprotein cholesterol levels in elderly patients hospitalized for heart failure with reduced ejection fraction

    Institute of Scientific and Technical Information of China (English)

    田甜; 徐予; 夏长伟; 张新雨

    2016-01-01

    Objective To observe the long - term relationship between levels of low - density lipoprotein cholesterol and post - discharge mortality among elderly patients hospitalized for heart failure with reduced ejection fraction(HFrEF). Methods This study was a single - center retrospective study. A total of 340 elderly HFrEF patients were included from August of 2007 to February of 2012. The cohort was divided into tertiles according to LDL - C levels:the low LDL - C level group(LDL - C≤2. 2667 mmol/ L),the moderate LDL - C level group( LDL - C 2. 873 3 mmol/ L ≤ )and the high LDL - C level group(LDL - C ﹥2. 873 3 mmol/ L). All - cause mortalities were compared. The impact of the different levels of LDL - C on all - cause mortality was analyzed by using multiariable Cox proportional hazards regression model. Results There were 116 all - cause deaths. All - cause mortality in the high LDL - C level group(23. 89%) was significantly lower than the moderate LDL - C level group( 36. 09%)and the low LDL - C level group( 43. 36%). Kaplan - Meier curves showed the all - cause mortality was lower in the high LDL - C level group than in the other two groups. According to the Cox proportional hazards regression model,the patients in the low LDL - C level group had a hazard ratio of all - cause death of 2. 135(95%CI:1. 311 ~3. 477,P = 0. 002)compared to those with high LDL - C level. Conclusion The high LDL - C levels were associated with a reduced post - discharge mortality among elderly patients hospitalized for HFrEF.%目的:研究血清低密度脂蛋白胆固醇(LDL - C)水平对老年住院射血分数降低性心力衰竭(HFrEF)患者长期预后的影响。方法本研究为单中心回顾性研究。选取2007年8月至2012年2月于郑州大学人民医院住院治疗的不同病因的340例老年 HFrEF 患者,依据血清 LDL - C 水平分为3组:低水平 LDL - C 组(LDL - C≤2.2667 mmol/ L),中等水平 LDL - C 组(LDL - C≤2.8733 mmol/ L

  10. Correlation of Friedewald's calculated low-density lipoprotein cholesterol levels with direct low-density lipoprotein cholesterol levels in a tertiary care hospital

    Science.gov (United States)

    Nanda, Sunil Kumar; Bharathy, M; Dinakaran, Asha; Ray, Lopamudra; Ravichandran, K

    2017-01-01

    Background: One of the risk factors for the development of coronary heart disease is high low-density lipoprotein (LDL) cholesterol levels. National Cholesterol Education Program ATP III guidelines suggest drug therapy to be considered at LDL-cholesterol levels >130 mg/dl. This makes accurate reporting of LDL cholesterol crucial in the management of Coronary heart disease. Estimation of LDL cholesterol by direct LDL method is accurate, but it is expensive. Hence, We compared Friedewald's calculated LDL values with direct LDL values. Aim: To evaluate the correlation of Friedewalds calculated LDL with direct LDL method. Materials and Methods: We compared LDL cholesterol measured by Friedewald's formula with direct LDL method in 248 samples between the age group of 20–70 years. Paired t-test was used to test the difference in LDL concentration obtained by a direct method and Friedewald's formula. The level of significance was taken as P values with Friedewald's formula. Results: There was no significant difference between the direct LDL values when compared to calculated LDL by Friedewalds formula (P = 0.140). Pearson correlation showed there exists good correlation between direct LDL versus Friedewalds formula (correlation coefficient = 0.98). The correlation between direct LDL versus Friedewalds calculated LDL was best at triglycerides values between 101 and 200 mg/dl. Conclusion: This study indicates calculated LDL by Friedewalds equation can be used instead of direct LDL in patients who cannot afford direct LDL method.

  11. Food combinations for cholesterol lowering.

    Science.gov (United States)

    Harland, Janice I

    2012-12-01

    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

  12. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to chitosan and reduction in body weight (ID 679, 1499), maintenance of normal blood LDL-cholesterol concentrations (ID 4663), reduction of intestinal transit time (ID

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to chitosan and reduction in body weight, maintenance of normal blood LDL-cholesterol concentrations, reduction of intestinal transit time and reduction of inflammation. The scientific substantiation is based on the information provided by the Member States in the consolidated list...... of Article 13 health claims and references that EFSA has received from Member States or directly from stakeholders. The food constituent that is the subject of the health claim is chitosan. The Panel considers that chitosan is sufficiently characterised....

  13. Scientific Opinion on the substantiation of a health claim related to the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol hexanicotinate in Limicol® and reduction of blood LDL-cholesterol concentrations pursuant to Article 14 of Regulation (EC No 1924/2006

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA

    2013-07-01

    Full Text Available Following an application from Laboratoire Lescuyer, submitted pursuant to Article 14 of Regulation (EC No 1924/2006 via the Competent Authority of France, the Panel on Dietetic Products, Nutrition and Allergies (NDA was asked to deliver an opinion on the scientific substantiation of a health claim related to the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol hexanicotinate in Limicol® and reduction of blood LDL-cholesterol concentrations. The Panel considers that the food which is the subject of the claim is sufficiently characterised. The Panel considers that reduction of blood LDL-cholesterol concentrations is a beneficial physiological effect. High LDL-cholesterol is a risk factor in the development of coronary heart disease. In weighing the evidence, the Panel took into account that, although no evidence was provided for an LDL-cholesterol lowering effect of any of the single food constituents in Limicol® at the proposed conditions of use or as to how the ingredients individually or in any combination could contribute to the claimed effect and despite the lack of a dose-response relationship observed in one human intervention study, three human intervention studies conducted by two independent research groups showed an effect of the combination of food ingredients in Limicol® on blood LDL-cholesterol concentrations. The Panel concludes that a cause and effect relationship has been established between the consumption of the combination of artichoke leaf dry extract standardised in caffeoylquinic acids, monacolin K in red yeast rice, sugar-cane derived policosanols, OPC from French maritime pine bark, garlic dry extract standardised in allicin, d-α-tocopheryl hydrogen succinate, riboflavin and inositol

  14. Scientific Opinion on the substantiation of a health claim related to OptiEFAX™ and maintenance of normal blood LDL-cholesterol concentrations pursuant to Article 13(5 of Regulation (EC No 1924/2006

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Dietetic Products, Nutrition and Allergies

    2012-07-01

    Full Text Available

    Following an application from Nutrilinks Sarl, submitted for authorisation of a claim pursuant to Article 13(5 of Regulation (EC No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA was asked to deliver an opinion on the scientific substantiation of a health claim related to OptiEFAX™ and maintenance of normal blood LDL-cholesterol concentrations. The food that is the subject of the health claim, OptiEFAX™, which is standardised pure krill oil, is sufficiently characterised in relation to the claimed effect. The claimed effect, maintenance of normal blood LDL-cholesterol concentrations, is a beneficial physiological effect. The target population proposed by the applicant is the general population. No human studies have been provided from which conclusions could be drawn for the scientific substantiation of the claim. A cause and effect relationship has not been established between the consumption of OptiEFAX™ and maintenance of normal blood LDL-cholesterol concentrations.

  15. [Study on LDL adsorbent modified by lauric acid].

    Science.gov (United States)

    Cong, Haixia; Du, Longbing; Fang, Bo; You, Chao

    2010-06-01

    A hydrophobic low-density lipoprotein cholesterol (LDL-C) adsorbent was synthesized with lauric acid and chitosan. The condition for adsorption was obtained by investigating the influence of adsorbent amount and adsorption time. The results of adsorption in vitro showed that the average adsorption rates for total cholesterol (TC), LDL-C, high-density lipoprotein cholesterol (HDL-C) and total protein (TP) were 47.7%, 84.7%, 18.1% and 5.9% respectively. The adsorbent possesses good selectivity in removing LDL-C.

  16. 去游离三酰甘油能否用于Friedewald公式计算LDL-C%To evaluate the feasibility of the concentration of low-density Hpoprotein cholesterol calculated by Friedewald formula based on the coricentration of free triglyceride

    Institute of Scientific and Technical Information of China (English)

    曾平; 陈曦; 刘运双

    2012-01-01

    目的 探讨去游离三酰甘油(TG)结果是否适用于Friedewald公式计算低密度脂蛋白胆固醇(LDL-C).方法 测定2820例血清样本总胆固醇(TC)、TG、高密度脂蛋白胆固醇(HDL-C)和LDL-C(方法1),将TG浓度>4.52mmol/L的结果剔除后,再用Friedewald公式计算剩余样本的LDL-C(方法2).根据TG浓度将剩余样本分成三组:一组TG为0.25~1.70mmol/L、二组TG为1.71 ~3.00mmol/L)、三组TG为3.01 ~4.52mmol/L,比较方法1与方法2所得LDL-C结果之间的差异.结果 一组两法所得LDL-C结果差异无统计学意义(P>0.05),其余两组LDL-C结果差异具有统计学意义(P<0.05).结论 TG浓度在0.25~1.70mmol/L范围内,可以使用Friedewald公式计算LDL-C.%Objective To investigate whether the concentration of the free triglyceride (TC) could use to calculate low-density llpoprotein cholesterol (LDL-C) with the Friedewald formula. Methods The serum concentration of the total cholesterol (TC), TG, high density lipoprotein cholesterol (HDL-C) and LDL-C(Method 1 ) were measured in 2820 patient*. The results of TC greater than 4.52mmol/L were removed. According to the concentration of TG, the others were divided into 3 groups, 0.25~1. 70mmol/L(group 1), 1.71~3.00 mmol/L(group 2) and 3.01~4.52 mmol/L( group 3), the LDL-C was calculated by the Friedewald formula (Method 2 ) in 3 groups. The difference of LDL-C between Method 1 and Method 2 were analyzed. Results The difference was not significant (P > 0. 05 ) in group 1. The difference was significant in the other two groups (P < 0.05 ). Conclusion The concentration of TG could not use to calculate the concentration of LDL-C with Friedewald formula, except the concentration of TG < 1.70mmol/L

  17. Does lycopene offer human LDL any protection against myeloperoxidase activity?

    Science.gov (United States)

    Chew, Poh Yeong; Riley, Lucy; Graham, Daniel L; Rahman, Khalid; Lowe, Gordon M

    2012-02-01

    Lycopene is a lipophilic antioxidant that is largely transported in human blood by Low Density Lipoproteins (LDL). One of the early events in the aetiology of atherosclerosis is thought to be the oxidation of LDL. Myeloperoxidase an enzyme secreted by neutrophils and macrophages is thought to oxidise human LDL particles. In this study, isolated human LDL was challenged with myeloperoxidase or copper, and the LDL was screened for lipoperoxidation and oxidation of apolipoprotein B100, depletion of lycopene and oxidation of cholesterol. Myeloperoxidase induced oxidation of LDL through direct interaction with apolipoprotein B100. No lipoperoxidation was observed following myeloperoxidase treatment; however, 7-ketocholesterol was detected indicating the products of myeloperoxidase interact with the surface of the LDL particles. Lycopene does react with the products of myeloperoxidase in solvent, but played no role in protecting against enzyme derived oxidation of human LDL.

  18. LDL-Apheresis: Technical and Clinical Aspects

    Directory of Open Access Journals (Sweden)

    Rolf Bambauer

    2012-01-01

    Full Text Available The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a levels, and coronary heart disease refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL apheresis is the therapeutic option. Today, there are five different LDL-apheresis systems available: cascade filtration or lipid filtration, immunoadsorption, heparin-induced LDL precipitation, dextran sulfate LDL adsorption, and the LDL hemoperfusion. There is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, sometimes the goal of therapy cannot be reached. Hence, in such patients, treatment with LDL-apheresis is indicated. Technical and clinical aspects of these five different LDL-apheresis methods are shown here. There were no significant differences with respect to or concerning all cholesterols, or triglycerides observed. With respect to elevated lipoprotein (a levels, however, the immunoadsorption method seems to be most effective. The different published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.

  19. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

  20. Low fatness, reduced fat intake and adequate plasmatic concentrations of LDL-cholesterol are associated with high bone mineral density in women: a cross-sectional study with control group

    Directory of Open Access Journals (Sweden)

    Sarkis Karin S

    2012-03-01

    Full Text Available Abstract Background Several parameters are associated with high bone mineral density (BMD, such as overweight, black background, intense physical activity (PA, greater calcium intake and some medications. The objectives are to evaluate the prevalence and the main aspects associated with high BMD in healthy women. Methods After reviewing the database of approximately 21,500 BMD scans performed in the metropolitan area of São Paulo, Brazil, from June 2005 to October 2010, high BMD (over 1400 g/cm2 at lumbar spine and/or above 1200 g/cm2 at femoral neck was found in 421 exams. Exclusion criteria were age below 30 or above 60 years, black ethnicity, pregnant or obese women, disease and/or medications known to interfere with bone metabolism. A total of 40 women with high BMD were included and matched with 40 healthy women with normal BMD, paired to weight, age, skin color and menopausal status. Medical history, food intake and PA were assessed through validated questionnaires. Body composition was evaluated through a GE-Lunar DPX MD + bone densitometer. Radiography of the thoracic and lumbar spine was carried out to exclude degenerative alterations or fractures. Biochemical parameters included both lipid and hormonal profiles, along with mineral and bone metabolism. Statistical analysis included parametric and nonparametric tests and linear regression models. P Results The mean age was 50.9 (8.3 years. There was no significant difference between groups in relation to PA, smoking, intake of calcium and vitamin D, as well as laboratory tests, except serum C-telopeptide of type I collagen (s-CTX, which was lower in the high BMD group (p = 0.04. In the final model of multivariate regression, a lower fat intake and body fatness as well a better profile of LDL-cholesterol predicted almost 35% of high BMD in women. (adjusted R2 = 0.347; p Conclusion Our results demonstrate the potential deleterious effect of lipid metabolism-related components, including

  1. 选择性抑制法测定血清低密度脂蛋白胆固醇诊断试剂盒评价%Evaluation of homogeneous LDL-cholesterol kit using selective inhibition method measure

    Institute of Scientific and Technical Information of China (English)

    谢松业; 丁星; 赵超; 陆元善

    2004-01-01

    [目的]用选择性抑制法原理测定和评价三种不同来源的低密度脂蛋白胆固醇(LDL-C)试剂盒的精密度、准确度、线性和抗干扰能力等试验.[方法]采用试剂盒提供的原程序,观察各剂盒的LDL-C测定的可靠性.[结果]实验结果表明,三种不同来源的LDL-C试剂盒均有良好的精密度,CV≤3.47%,并具有较好的抗溶血(Hb:2.5~20g/L)抗黄疸(胆红素:42.8~342μmol/L),和抗脂浊(TG:2.85~13.1mol/L)的能力,准确性除了Randox高浓度(LDL-C5.736~7.17mmol/L)不准性为22~33%外,BM、和光公司LDL-C测得(LDL-C 0.71~7.17mmol/L)不准确性均<6%.线性回归方程(LDL-C为0.717~10.755mmol/L)及相关系数分别是:Randox为Y=1.3024x-0.51,r=0.998.BM为Y=1.065x-0.5923,r=0.9956.各光公司Y=0.9614x-0.1273,r=0.9981.[结论]三种不同来源的LDL-C试剂盒回收率也较令人满意.

  2. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to the raw fruit of Emblica officinalis Gaertn. and maintenance of normal blood LDL-cholesterol concentrations (ID 4041) and protection of DNA, proteins and lipids from

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to the raw fruit of Emblica officinalis Gaertn. and maintenance of normal blood LDL-cholesterol concentrations and protection of DNA, proteins and lipids from oxidative damage. The scientific substantiation is based on the information provided by the Member States in the consolidated...

  3. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to OptiEFAX™ and maintenance of normal blood LDL-cholesterol concentrations pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    Following an application from Nutrilinks Sarl, submitted for authorisation of a claim pursuant to Article 13(5) of Regulation (EC) No 1924/2006 via the Competent Authority of Belgium, the Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific...... of normal blood LDL-cholesterol concentrations, is a beneficial physiological effect. The target population proposed by the applicant is the general population. No human studies have been provided from which conclusions could be drawn for the scientific substantiation of the claim. A cause and effect...

  4. Small dense low density lipoprotein cholesterol and coronary heart disease: results from the Framingham Offspring Study

    Science.gov (United States)

    We sought to establish reference values for a new direct assay for small dense LDL cholesterol (sdLDL-C) and to measure sdLDL-C concentrations in patients with established coronary heart disease (CHD) vs controls. Direct LDL-C and sdLDL-C were measured in samples from 3188 male and female participan...

  5. 阿托伐他汀不同服药方法对血清低密度脂蛋白胆固醇的影响%Effect of every other day dose atorvastatin on serum LDL-cholesterol

    Institute of Scientific and Technical Information of China (English)

    李华; 陈林祥; 余泽洪

    2009-01-01

    目的 比较阿托伐他汀(立普妥)隔日口服与每日口服20 mg对血清低密度脂蛋白胆固醇(LDL-C)的疗效.方法 对132例LDL-C升高的患者,前瞻、随机、非双盲分为每日口服组与隔日服药组.两组服药前剂量为20 mg.LDL-C>3.37 mmol/L(130mg/dl)为入选对象.在治疗前及治疗2个月后测LDL-C及高密度脂蛋白胆固醇(HDL-C)、总胆固醇(CT)、甘油三脂(TG)并进行对比,同时测谷丙转氨酶(SGPT)、谷草转氨酶(SGOT)、肌酸磷酸激酶(CK)及了解其他副作用.结果经治疗2个月后LDL-C水平均明显降低,LDL-C水平降低程度,隔日服药组为35.6%,每日服药组为38.5%,两组降低水平差异无统计学意义(P>0.05), SGPT,SGOT,Cre,CK及其他副作用差异无统计学意义(P<0.05).结论 阿托伐他汀隔日口服或每日口服药20 mg对降低LDL-C水平相似,副作用亦相似,但隔日服药降低了医疗费用并提高了服药依从性.

  6. LDL and HDL subfractions, dysfunctional HDL: treatment options.

    Science.gov (United States)

    Garcia-Rios, Antonio; Nikolic, Dragana; Perez-Martinez, Pablo; Lopez-Miranda, Jose; Rizzo, Manfredi; Hoogeveen, Ron C

    2014-01-01

    Low-density lipoproteins (LDL) are considered as important risk factors for cardiovascular diseases (CVD), while highdensity lipoproteins (HDL) are well recognized for their putative role in reverse cholesterol transport and other atheroprotective functions. Both LDL and HDL are heterogeneous in nature, including various subfractions depending on the method of isolation (≥ 7 LDL and 10 HDL subspecies, respectively). While it is established that small, dense LDL (sdLDL) have atherogenic potential, the role of different HDL subfractions is still largely unclear. The majority of clinical studies suggest an atheroprotective role of larger HDL particles, although recent work has highlighted the role of dysfunctional HDL within different subfractions. Several therapeutic approaches are able to primarily target cholesterol concentration in LDL or HDL. Certain drugs, such as niacin, statins and fibrates target multiple lipid traits (i.e. pleiotropic drug effects), while cholesterol ester transfer protein (CETP) inhibitors are able to increase plasma HDL cholesterol levels. Statins represent the most used lipid-lowering drugs, but there is a continued interest in the development of novel therapeutic approaches, including those that might affect dysfunctional HDL. Targeting distinct LDL and HDL subfractions may potentially reduce the residual risk seen in clinical endpoint trials.

  7. Cholesterol oxides inhibit cholesterol esterification by lecithin: cholesterol acyl transferase

    Directory of Open Access Journals (Sweden)

    Eder de Carvalho Pincinato

    2009-09-01

    Full Text Available Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC 2.3.1.43 and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL to low density lipoproteins (LDL and very low density lipoproteins (VLDL by cholesteryl ester transfer protein (CETP was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and thereby disturbing

  8. Are You Taking the Right Treatment for Your High Cholesterol?

    Science.gov (United States)

    ... you taking the right treatment for your high cholesterol? Our analysis and new guidelines could change your ... people consider a moderate-intensity statin (reduces LDL cholesterol by 30 percent to 50 percent) • People 40 ...

  9. Clinic application of serum low-density lipoprotein cholesterol level in predicting expansion hematoma in elderly male patients with acute hypertensive intracerebral hemorrhage%血清LDL-C水平对老年男性高血压性脑出血血肿扩大的预测作用

    Institute of Scientific and Technical Information of China (English)

    周红霞; 刘首峰; 李玉旺; 王欣; 徐小林

    2015-01-01

    Objective To investigate whether serum level of low-density lipoprotein cholesterol can predict the expan⁃sion of hemorrhage growth in elderly male patients with acute hypertensive intracerebral hemorrhage. Methods Patients (n=108) who visited our hospital with from June 2012 until May 2014 spontaneous hypertensive intracerebral hemorrhage with⁃in 6 hours of onset which is confirmed by initial computed tomography (CT) were sent to repeated CT within 24 hours of on⁃set. All selected patients were divided into the LDL-C≥2.49 mmol/L group and LDL-C<2.49 mmol/L group. Clinical data of these 2 groups were compared and the relationships of hematoma growth and its risk factors were analyzed. Results Baseline blood pressure, the level of blood glucose, PT, APTT, FIB, PLT and hemorrhage volume did not differ significantly between the LDL-C≥2.49 mmol/L group and LDL-C<2.49 mmol/L group. The ratio of hemorrhage growth in LDL-C<2.49 mmol/L group was significantly higher than that in LDL-C≥2.49 mmol/L group (34.21%vs 11.43%). Multiple logistic regres⁃sion analysis showed that LDL-C<2.49 mmol/L was the only risk factor contribute to hemorrhage growth. Conclusion Pa⁃tients with LDL-C<2.49 mmol/L in acute intracerebral hemorrhage are of high risk of hemorrhage growth so early attention and appropriate procedure are needed to prevent or slow its growth.%目的:探讨血清低密度脂蛋白胆固醇(LDL-C)水平对老年男性高血压性脑出血急性期血肿扩大有无预测作用。方法收集我院2012年6月—2014年5月发病6 h以内的老年男性高血压性脑出血患者108例,按发病时LDL-C水平分为LDL-C<2.49 mmol/L组和LDL-C≥2.49 mmol/L组,对2组患者入院时的收缩压(SBP)、舒张压(DBP)、血糖水平、凝血酶原时间(PT)、部分活化凝血酶时间(APTT)、纤维蛋白原(FIB)、血小板计数、血肿体积进行对比分析,并于发病24 h复查头CT了解2组血肿扩大情况并进

  10. 微粒化非诺贝特和洛代他汀对老年人低高密度脂蛋白胆固醇(HDL-ch)和高低密度脂蛋白(LDL-ch)的疗效比较%A Comparison of the Therapeutic Effects of Comicromised Fenofibrate with Lovastatin in the Treatment of Eldly with Low High-density Lipoprotein(HDL) Cholesterol and Elevated Low-density Lipoprotein(LDL) Cholesterol

    Institute of Scientific and Technical Information of China (English)

    施行舟; 叶志荣

    2002-01-01

    为了比较微粒化非诺贝特和洛伐他汀对低HDL-ch和高LDL -ch的疗效,将80例低HDL伴高LDL的老年唤者随机分为非诺贝特组和洛代他汀组,每组各40例,分别予服用微粒化非诺贝特和洛代他汀,疗程为12周.结果发现非诺贝特组于治疗后8周即可有显著的升高HDL-ch,且疗效随疗程的增加而增加,而洛伐他汀组仅有轻度升高HDL-ch作用,尚未达到显著性水平,二组疗效相比,具有显著性意义(P=0.0271).非洛贝特组和洛伐他汀组于治疗后4周都可以显著降低LDL(P<0.05),且疗效都随着疗程的增加而增加,二组疗效相比,尚未达到显著性水平(P=0.0785).因此,微粒化非诺贝特可升高老年患者的HDL-ch,降低LDL-ch水平,而洛伐他门仅能够显著降低患者的LDL-ch水平,对于同时伴有低HDL-ch和高LDL-ch老年患者,应首先考虑选择非诺贝特进行降脂治疗.

  11. A homogeneous assay of HKL-and LDL-cholesterol and its technological requirements%高、低密度脂蛋白胆固醇的匀相测定法及技术要求

    Institute of Scientific and Technical Information of China (English)

    鄢盛恺

    2002-01-01

    @@ 流行病学与临床研究证实,动脉粥样硬化(AS)、冠心病的发生率与血清高密度脂蛋白胆固醇(HDL-C)水平呈负相关,而与低密度脂蛋白胆固醇(LDL-C)水平呈正相关.美国国家胆固醇教育计划(NCEP)成人治疗专家组(ATP)新近发表的第3版文件(ATPⅢ,2001年)修改了血脂、脂蛋白水平异常的分类,低HDL-C[<1.04 mmol/L(40 mg/dl)]是冠心病的主要危险因素,而高HDL-C[≥1.56 mmol/L(60 mg/dl)]被认为是负危险因子,具有保护性.将LDL-C新划分为5个水平,仍以降低LDL-C水平作为冠心病防治的首要目标[1].

  12. HELP LDL apheresis reduces plasma pentraxin 3 in familial hypercholesterolemia.

    Directory of Open Access Journals (Sweden)

    Michela Zanetti

    Full Text Available BACKGROUND: Pentraxin 3 (PTX3, a key component of the humoral arm of innate immunity, is secreted by vascular cells in response to injury, possibly aiming at tuning arterial activation associated with vascular damage. Severe hypercholesterolemia as in familial hypercholesterolemia (FH promotes vascular inflammation and atherosclerosis; low-density lipoprotein (LDL apheresis is currently the treatment of choice to reduce plasma lipids in FH. HELP LDL apheresis affects pro- and antiinflammatory biomarkers, however its effects on PTX3 levels are unknown. We assessed the impact of FH and of LDL removal by HELP apheresis on PTX3. METHODS: Plasma lipids, PTX3, and CRP were measured in 19 patients with FH undergoing chronic HELP LDL apheresis before and after treatment and in 20 control subjects. In the patients assessment of inflammation and oxidative stress markers included also plasma TNFα, fibrinogen and TBARS. RESULTS: At baseline, FH patients had higher (p = 0.0002 plasma PTX3 than matched control subjects. In FH PTX3 correlated positively (p≤0.05 with age, gender and CRP and negatively (p = 0.01 with HELP LDL apheresis vintage. The latter association was confirmed after correction for age, gender and CRP. HELP LDL apheresis acutely reduced (p≤0.04 plasma PTX3, CRP, fibrinogen, TBARS and lipids, but not TNFα. No association was observed between mean decrease in PTX3 and in LDL cholesterol. PTX3 paralleled lipids, oxidative stress and inflammation markers in time-course study. CONCLUSION: FH is associated with increased plasma PTX3, which is acutely reduced by HELP LDL apheresis independently of LDL cholesterol, as reflected by the lack of association between change in PTX3 and in LDL levels. These results, together with the finding of a negative relationship between PTX3 and duration of treatment suggest that HELP LDL apheresis may influence both acutely and chronically cardiovascular outcomes in FH by modulating PTX3.

  13. In vivo regulation of hepatic LDL receptor mRNA in the baboon. Differential effects of saturated and unsaturated fat.

    Science.gov (United States)

    Fox, J C; McGill, H C; Carey, K D; Getz, G S

    1987-05-25

    The effects of diets enriched with cholesterol and different fats upon plasma lipoproteins and hepatic low density lipoprotein (LDL) receptor mRNA levels were studied in a group of 18 normal baboons. Animals were fed diets containing 1% cholesterol and 25% fat as either coconut oil, peanut oil, or olive oil for a period of 20 weeks. Plasma total cholesterol, high density lipoprotein (HDL) cholesterol, beta-lipoprotein (LDL + very low density lipoprotein) cholesterol, apolipoprotein B and apolipoprotein A-I were measured in samples obtained at 4-week intervals. All three diet groups demonstrated a statistically significant increase in plasma cholesterol as compared to base line throughout the experiment. Hepatic LDL receptor (LDL-R) mRNA levels were quantified by dot blot hybridization in serial liver biopsies. Animals fed saturated fat sustained a significant reduction in hepatic LDL-R mRNA as compared to those fed either monounsaturated or polyunsaturated fat. A strong negative correlation between LDL-R mRNA and plasma total cholesterol (r = -0.71), HDL cholesterol (r = -0.76), and plasma apo A-I (r = -0.77) was observed only in those animals fed coconut oil. Weak negative correlations between LDL-R mRNA and other plasma parameters did not achieve statistical significance. We conclude that saturated and unsaturated oils may influence plasma cholesterol levels in part through differential effects on LDL receptor biosynthesis in baboons.

  14. Reduction in intestinal cholesterol absorption by various food components: mechanisms and implications.

    Science.gov (United States)

    Cohn, Jeffrey S; Kamili, Alvin; Wat, Elaine; Chung, Rosanna W S; Tandy, Sally

    2010-06-01

    A number of different food components are known to reduce plasma and LDL-cholesterol levels by affecting intestinal cholesterol absorption. They include: soluble fibers, phytosterols, saponins, phospholipids, soy protein and stearic acid. These compounds inhibit cholesterol absorption by affecting cholesterol solubilization in the intestinal lumen, interfering with diffusion of luminal cholesterol to the gut epithelium and/or inhibiting molecular mechanisms responsible for cholesterol uptake by the enterocyte. Cholesterol content of intestinal chylomicrons is subsequently reduced, less cholesterol is transported to the liver within chylomicron remnants, hepatic LDL-receptor activity is increased and plasma levels of LDL-cholesterol are decreased. Reduced hepatic VLDL production and less conversion of VLDL to LDL also contribute to lower LDL levels. Certain food components may also affect intestinal bile acid metabolism. Further investigation of the way in which these functional ingredients affect intestinal lipid metabolism will facilitate their use and application as cardiovascular nutraceuticals.

  15. The serum levels of total cholesterol and LDL-cholesterol in prognostic effect for breast tumor%血清总胆固醇及低密度脂蛋白水平对乳腺癌预后的影响

    Institute of Scientific and Technical Information of China (English)

    林晓榕; 黄迪; 陈静琦; 吴智勇

    2015-01-01

    目的 探讨血清中脂蛋白水平对乳腺癌预后的影响.方法 回顾分析2003年11月至2008年9月在中山大学孙逸仙纪念医院初诊的244例乳腺癌患者及同期99例健康体者的临床资料.比较两者血清代谢指标的变化,Spearman相关分析总胆固醇、LDL-C与乳腺癌的肿瘤大小的关系,Cox回归模型评估影响无病生存率(DFS)的预后因素.结果 乳腺癌患者血清总胆固醇(TC)、甘油三酯、低密度脂蛋白(LDL-C)、血糖较正常人高,而高密度脂蛋白(HDL-C)较正常人低;血清总胆固醇、LDL-C水平在ER/PR阳性乳腺癌患者中较Her-2阳性及三阴型乳腺癌低.血清总胆固醇、LDL-C与肿瘤的大小呈正相关.TC≥5.2 mmol/L组或LDL-C>3.08 mmol/L组的DFS较TC<5.2 mmol/L组或LDL-C≤3.08mmol/L组明显降低(TC 68% vs 77.7%,LDL-C 73.4%vs 86.3%,P<0.05).结论 高胆固醇、高LDL-C血症是乳腺癌独立的预后因素.

  16. 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...

  17. Walnut-enriched diet increases the association of LDL from hypercholesterolemic men with human HepG2 cells.

    Science.gov (United States)

    Muñoz, S; Merlos, M; Zambón, D; Rodríguez, C; Sabaté, J; Ros, E; Laguna, J C

    2001-12-01

    In a randomized, cross-over feeding trial involving 10 men with polygenic hypercholesterolemia, a control, Mediterranean-type cholesterol-lowering diet, and a diet of similar composition in which walnuts replaced approximately 35% of energy from unsaturated fat, were given for 6 weeks each. Compared with the control diet, the walnut diet reduced serum total and LDL cholesterol by 4.2% (P = 0.176), and 6.0% (P = 0.087), respectively. No changes were observed in HDL cholesterol, triglycerides, and apolipoprotein A-I levels or in the relative proportion of protein, triglycerides, phospholipids, and cholesteryl esters in LDL particles. The apolipoprotein B level declined in parallel with LDL cholesterol (6.0% reduction). Whole LDL, particularly the triglyceride fraction, was enriched in polyunsaturated fatty acids from walnuts (linoleic and alpha-linolenic acids). In comparison with LDL obtained during the control diet, LDL obtained during the walnut diet showed a 50% increase in association rates to the LDL receptor in human hepatoma HepG2 cells. LDL uptake by HepG2 cells was correlated with alpha-linolenic acid content of the triglyceride plus cholesteryl ester fractions of LDL particles (r(2) = 0.42, P < 0.05). Changes in the quantity and quality of LDL lipid fatty acids after a walnut-enriched diet facilitate receptor-mediated LDL clearance and may contribute to the cholesterol-lowering effect of walnut consumption.

  18. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to 3 g/day plant stanols as plant stanol esters and lowering blood LDL-cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC

    DEFF Research Database (Denmark)

    Tetens, Inge

    related to 3 g/day plant stanols as plant stanol esters per day and lowering blood LDL-cholesterol by 12 % and reduced risk of (coronary) heart disease. The applicant has further requested that the minimum duration to obtain the effect be stated to be one to two weeks, and that the claims be authorised...... for an extended range of foods, including yellow fat spreads, dairy products, cheese, rye bread, oatmeal, fermented soy milk based products (drinkable and spoonable yoghurt-type products), and oat based milk drinks. The applicant provided an unpublished meta-analysis with 18 randomised, controlled human studies...... on the LDL-lowering efficacy of plant stanol esters at intakes between 2.7 to 3.3 g per day plant stanols. On the basis of the data presented, the Panel concludes that plant stanol esters at a daily intake of 3 g plant stanols (range 2.7 g to 3.3 g) in matrices approved by Regulation (EC) No 376/2010 (yellow...

  19. The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review.

    Science.gov (United States)

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Goulet, Amy; Moghadasian, Mohammed H

    2016-10-25

    Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.

  20. 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...

  1. Regulation of cholesterol synthesis in four colonic adenocarcinoma cell lines.

    Science.gov (United States)

    Cerda, S R; Wilkinson, J; Broitman, S A

    1995-12-01

    Colon tumor cells, unlike normal human fibroblasts, exhibited an uncoupling of low density lipoprotein (LDL)-derived cholesterol from cellular growth, when endogenous cholesterol synthesis was inhibited by mevinolin, a hydroxymethylglutaryl-CoA reductase (HMG-CoAR) competitive inhibitor [Fabricant, M., and Broitman, S.A. (1990) Cancer Res. 50, 632-636]. Further evaluation of cholesterol metabolism was conducted in two undifferentiated (SW480, SW1417) and two differentiated (HT29, CACO2) colonic adenocarcinoma (adeno-CA) cell lines and an untransformed human fibroblast, AG1519A. Cells grown in monolayer culture to near subconfluency were used to assess endogenous cholesterol synthesis by 14C-acetate incorporation, in response to the following treatments in lipoprotein-deficient serum (LPDS)-supplemented minimum essential medium (MEM): LPDS alone, LDL, mevinolin, mevinolin with LDL, and 25-hydroxy-cholesterol (25-OH-CH). Complete fetal bovine serum (FBS)-supplemented MEM was used as control. All colon tumor lines exhibited similarly high endogenous cholesterol synthesis in both FBS and LPDS relative to the fibroblasts which demonstrated low basal levels in FBS and maximal synthesis in LPDS. LDL treatment did not inhibit cholesterol synthesis in colon tumor cells, but suppressed that in the fibroblast by 70%. Sterol repression of cholesterol synthesis mediated by 25-OH-CH occurred in all cells. Mevinolin caused a reduction in cholesterol synthesis in the colonic cancer cell lines, which was not further decreased by concurrent addition of LDL. In contrast, in mevinolin-treated fibroblasts, LDL further inhibited cholesterol synthesis. When the effect of cell density on cholesterol synthesis regulation was evaluated under conditions of sparse density in SW480 and SW147, results indicated that (i) basal rates of cholesterol synthesis were higher, (ii) LDL inhibited cholesterol synthesis more effectively, and (iii) mevinolin or 25-OH-CH had a more pronounced effect than in

  2. Cholesterol Test

    Science.gov (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Cholesterol Share this page: Was this page helpful? Also known as: Blood Cholesterol Formal name: Total Cholesterol Related tests: HDL Cholesterol , ...

  3. What's Cholesterol?

    Science.gov (United States)

    ... los dientes Video: Getting an X-ray What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? Print A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  4. What's Cholesterol?

    Science.gov (United States)

    ... Room? What Happens in the Operating Room? What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? A A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  5. Smallest LDL particles are most strongly related to coronarydisease progression in men

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Paul T.; Superko, H. Robert; Haskell, William L.; Alderman, Edwin L.; Blanche, Patricia J.; Holl, Laura Glines; Krauss,Ronald M.

    2002-12-03

    Objective-LDLs include particle subclasses that havedifferent mobilities on polyacrylamide gradient gels: LDL-I (27.2to 28.5nm), LDL-IIa (26.5 to 27.2 nm), LDL-IIb (25.6 to 26.5 nm), LDL-IIIa (24.7to 25.6 nm), LDL-IIIb (24.2 to 24.7nm), LDL-IVa (23.3 to 24.2 nm), andLDL-IVb (22.0 to 23.3 nm in diameter). We hypothesized that theassociationbetween smaller LDL particles and coronary artery disease(CAD) risk might involve specific LDL subclasses.Methods andResults-Average 4-year onstudy lipoprotein measurements were comparedwith annualized rates of stenosischange from baseline to 4 years in 117men with CAD. The percentages of total LDL and HDL occurringwithinindividual subclasses were measured by gradient gelelectrophoresis. Annual rate of stenosis change was relatedconcordantlyto onstudy averages of total cholesterol (P 0.04), triglycerides (P0.05), VLDL mass (P 0.03),total/HDL cholesterol ratio (P 0.04), LDL-IVb(P 0.01), and HDL3a (P 0.02) and inversely to HDL2-mass (P 0.02)and HDL2b(P 0.03). The average annual rate in stenosis change was 6-fold morerapid in the fourth quartile ofLDL-IVb (5.2 percent) than in the firstquartile ( 2.5 percent, P 0.03). Stepwise multiple regression analysisshowed thatLDL-IVb was the single best predictor of stenosischange.Conclusions-LDL-IVb was the single best lipoprotein predictor ofincreased stenosis, an unexpected result, given thatLDL-IVb representsonly a minor fraction of total LDL. (Arterioscler Thromb Vasc Biol.2003;23:314-321.)

  6. LDL uptake by Leishmania amazonensis: involvement of membrane lipid microdomains.

    Science.gov (United States)

    De Cicco, Nuccia N T; Pereira, Miria G; Corrêa, José R; Andrade-Neto, Valter V; Saraiva, Felipe B; Chagas-Lima, Alessandra C; Gondim, Katia C; Torres-Santos, Eduardo C; Folly, Evelize; Saraiva, Elvira M; Cunha-E-Silva, Narcisa L; Soares, Maurilio J; Atella, Georgia C

    2012-04-01

    Leishmania amazonensis lacks a de novo mechanism for cholesterol synthesis and therefore must scavenge this lipid from the host environment. In this study we show that the L. amazonensis takes up and metabolizes human LDL(1) particles in both a time and dose-dependent manner. This mechanism implies the presence of a true LDL receptor because the uptake is blocked by both low temperature and by the excess of non-labelled LDL. This receptor is probably associated with specific microdomains in the membrane of the parasite, such as rafts, because this process is blocked by methyl-β-cyclodextrin (MCBD). Cholesteryl ester fluorescently-labeled LDL (BODIPY-cholesteryl-LDL) was used to follow the intracellular distribution of this lipid. After uptake it was localized in large compartments along the parasite body. The accumulation of LDL was analyzed by flow cytometry using FITC-labeled LDL particles. Together these data show for the first time that L. amazonensis is able to compensate for its lack of lipid synthesis through the use of a lipid importing machinery largely based on the uptake of LDL particles from the host. Understanding the details of the molecular events involved in this mechanism may lead to the identification of novel targets to block Leishmania infection in human hosts.

  7. Impacto do exercício físico isolado e combinado com dieta sobre os níveis séricos de HDL, LDL, colesterol total e triglicerídeos Impact of isolated and combined with diet physical exercise on the HDL, LDL, total cholesterol and triglycerides plasma levels

    Directory of Open Access Journals (Sweden)

    Sanmira Fagherazzi

    2008-08-01

    Full Text Available Adequados hábitos alimentares e a prática de exercícios físicos exercem efeito benéfico sobre as dislipidemias. Se associados, podem ainda otimizar as mudanças do perfil lipoprotéico plasmático, sendo, além disso, intervenções de custo moderado quando comparados com tratamentos medicamentosos e dependentes de alta tecnologia. Este estudo tem por objetivo avaliar o impacto do exercício físico isolado e combinado com dieta sobre o perfil lipídico em indivíduos com sobrepeso/obesos. O presente trabalho é do tipo retrospectivo analítico observacional. Nele foi analisada a evolução do perfil lipídico e do peso, por período entre três e seis meses, de 30 indivíduos, divididos em dois grupos: grupo exercício (prática de exercício físico e grupo dieta (prática de exercício físico associada à intervenção nutricional. Foram encontradas reduções estatisticamente significativas no CT (-14,4mg/dl; P = 0,022 e no LDL-c (-20,9mg/dl; P = 0,013 para os componentes do grupo exercício. Tal redução também ocorreu em relação à razão CT/HDL-c (-0,9; P = 0,005 para os componentes do grupo dieta. Foi observada elevação dos níveis de HDL-c, apenas no grupo dieta (+4,2 mg/dl. Nesse mesmo grupo verificou-se diminuição no CT (-8mg/dl e no LDL-c (-9,8mg/dl, bem como redução de peso (-2,6kg, no entanto, tais resultados não foram estatisticamente significativos. Quanto aos níveis de TG, não foi verificada evolução positiva em ambos os grupos. Concluiu-se que o efeito isolado do exercício físico foi mais evidente em relação às variáveis CT e LDL-c. Os TG não sofreram modificações positivas com a prática exclusiva de exercícios físicos ou com sua associação à dieta. Para as variáveis HDL-c e peso, a combinação da dieta com o exercício físico apresentou maiores benefícios.Adequate eating habits and physical exercise have a beneficial effect on dislipidemies. When associated, they might even optimize

  8. 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 o

  9. Longevity-associated NADH Dehydrogenase Subunit-2 237 Leu/Met Polymorphism Modulates the Effects of Daily Alcohol Drinking on Yearly Changes in Serum Total and LDL Cholesterol in Japanese Men

    Directory of Open Access Journals (Sweden)

    Takashima,Yutaka

    2009-12-01

    Full Text Available Reduced nicotinamide adenine dinucleotide (NADH dehydrogenase subunit 2 237 leucine/methionine (ND2-237 Leu/Met polymorphism, is reportedly associated with longevity in the Japanese population. The ND2-237Met genotype may exert resistance to atherogenic diseases, such as myocardial infarction or cerebrovascular disorders. To investigate whether ND2-237 Leu/Met polymorphism is associated with yearly changes in serum lipid levels, we conducted a longitudinal study of 107 healthy Japanese male subjects. Analysis of covariance revealed that the interaction between the ND2-237 Leu/Met genotypes and habitual drinking was significantly associated with yearly changes in serum total cholesterol (TC and low-density lipoprotein cholesterol (LDLC levels (p0.036 and p0.006, respectively. In multiple regression analysis, daily drinking was significantly and positively associated with yearly changes in serum LDLC levels in men with ND2-237Met (p0.026. After adjusting for covariates, yearly changes in serum LDLC levels were significantly lower in non-daily drinkers with ND2-237Met than in those with ND2-237Leu (p0.047. These results suggest that ND2-237Met has a beneficial impact on yearly changes in serum LDLC in non-daily drinkers but not in daily drinkers.

  10. Effect of doxazosin on cholesterol synthesis in cell culture

    Energy Technology Data Exchange (ETDEWEB)

    D' Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent.

  11. [The LDL receptor family].

    Science.gov (United States)

    Meilinger, Melinda

    2002-12-29

    The members of the LDL receptor family are structurally related endocytic receptors. Our view on these receptors has considerably changed in recent years. Not only have new members of the family been identified, but also several interesting observations have been published concerning the biological function of these molecules. The LDL receptor family members are able to bind and internalize a plethora of ligands; as a consequence, they play important roles in diverse physiological processes. These receptors are key players in the lipoprotein metabolism, vitamin homeostasis, Ca2+ homeostasis, cell migration, and embryonic development. Until recently, LDL receptor family members were thought to be classic endocytic receptors that provide cells with metabolites on one hand, while regulating the concentration of their ligands in the extracellular fluids on the other hand. However, recent findings indicate that in addition to their cargo transport function, LDL receptor family members can act as signal transducers, playing important roles in the development of the central nervous system or the skeleton. Better understanding of physiological and pathophysiological functions of these molecules may open new avenues for the treatment or prevention of many disorders.

  12. Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.

    Science.gov (United States)

    Viola, Manuela; Bartolini, Barbara; Vigetti, Davide; Karousou, Evgenia; Moretto, Paola; Deleonibus, Sara; Sawamura, Tatsuya; Wight, Thomas N; Hascall, Vincent C; De Luca, Giancarlo; Passi, Alberto

    2013-10-11

    Thickening of the vessel in response to high low density lipoprotein(s) (LDL) levels is a hallmark of atherosclerosis, characterized by increased hyaluronan (HA) deposition in the neointima. Human native LDL trapped within the arterial wall undergoes modifications such as oxidation (oxLDL). The aim of our study is to elucidate the link between internalization of oxLDL and HA production in vitro, using human aortic smooth muscle cells. LDL were used at an effective protein concentration of 20-50 μg/ml, which allowed 80% cell viability. HA content in the medium of untreated cells was 28.9 ± 3.7 nmol HA-disaccharide/cell and increased after oxLDL treatment to 53.9 ± 5.6. OxLDL treatments doubled the transcripts of HA synthase HAS2 and HAS3. Accumulated HA stimulated migration of aortic smooth muscle cells and monocyte adhesiveness to extracellular matrix. The effects induced by oxLDL were inhibited by blocking LOX-1 scavenger receptor with a specific antibody (10 μg/ml). The cholesterol moiety of LDL has an important role in HA accumulation because cholesterol-free oxLDL failed to induce HA synthesis. Nevertheless, cholesterol-free oxLDL and unmodified cholesterol (20 μg/ml) induce only HAS3 transcription, whereas 22,oxysterol affects both HAS2 and HAS3. Moreover, HA deposition was associated with higher expression of endoplasmic reticulum stress markers (CHOP and GRP78). Our data suggest that HA synthesis can be induced in response to specific oxidized sterol-related species delivered through oxLDL.

  13. HDL cholesterol as a residual risk factor for vascular events and all cause mortality in patients with type 2 diabetes

    NARCIS (Netherlands)

    Sharif, Shahnam; Van Der Graaf, Yolanda; Nathoe, Hendrik M.; de Valk, Harold W.; Visseren, Frank L J; Westerink, Jan

    2016-01-01

    OBJECTIVE: To evaluate whether low HDL cholesterol (HDL-c) levels are a risk factor for cardiovascular disease and mortality in patients with type 2 diabetes and whether it remains a residual risk factor when attaining low LDL cholesterol (LDL-c) treatment goals or when LDL-c is treated with intensi

  14. [Utility of treatment with atorvastatin 40 mg plus ezetimibe 10 mg versus atorvastatin 80 mg in reducing the levels of LDL cholesterol in patients with ischaemic stroke or transient ischaemic attack].

    Science.gov (United States)

    Palacio, Enrique; Viadero-Cervera, Raquel; Revilla, Marián; Larrosa-Campo, Davinia; Acha-Salazar, Olga; Novo-Robledo, Francisco; Oterino, Agustín

    2016-03-01

    Introduccion. Tras un ictus isquemico, reducir los niveles de colesterol LDL (LDLc) disminuye el riesgo de recurrencia. El riesgo de recurrencia es menor con reducciones mas intensas de las cifras de LDLc. Objetivo. Evaluar la eficacia y seguridad del tratamiento hipolipemiante combinado con atorvastatina 40 mg mas ezetimiba 10 mg tras un ictus isquemico o ataque isquemico transitorio (AIT). Pacientes y metodos. Evaluacion de la eficacia del tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg (n = 34) frente a atorvastatina 80 mg (n = 52) en la modificacion de parametros lipidicos tras un ictus isquemico o AIT. Se establecio como objetivo primario la obtencion de niveles de LDLc = 50%. Adicionalmente se evaluo la presencia de efectos secundarios en ambos grupos. Resultados. Se observo un incremento significativo de las probabilidades de alcanzar el objetivo primario en el grupo tratado con atorvastatina 40 mg mas ezetimiba 10 mg (odds ratio: 11,94; intervalo de confianza al 95%: 2,82-50,64; p = 0,001) y en los varones (odds ratio: 4,76; intervalo de confianza al 95%: 1,35-16,67; p = 0,02). El tratamiento con atorvastatina 40 mg mas ezetimiba 10 mg obtuvo reducciones superiores de LDLc (p probabilidad de alcanzar los objetivos de LDLc. Ambos tratamientos son seguros y bien tolerados.

  15. Altered Metabolism of LDL in the Arterial Wall Precedes Atherosclerosis Regression

    DEFF Research Database (Denmark)

    Bartels, Emil D.; Christoffersen, Christina; Lindholm, Marie W.

    2015-01-01

    Rationale: Plasma cholesterol lowering is beneficial in patients with atherosclerosis. However, it is unknown how it affects entry and degradation of low-density lipoprotein (LDL) particles in the lesioned arterial wall. Objective: We studied the effect of lipid-lowering therapy on LDL permeability...

  16. The Effect of LDL-Apheresis and Rheohaemapheresis Treatment on Vitamin E.

    Science.gov (United States)

    Solichová, Dagmar; Bláha, Milan; Aufartová, Jana; Krcmová, Lenka Kujovská; Plíšek, Jirí; Honegrová, Barbora; Kasalová, Eva; Lánská, Miriam; Urbánek, Lubor; Sobotka, Luboš

    2015-01-01

    Lipid apheresis (extracorporeal lipoprotein elimination) is administered to patients with familial hypercholesterolemia who fail to respond to standard therapy. The nature of the treatment process raises the suspicion that it decreases not only cholesterol but also antioxidants. A group of 12 patients (average age 47±17 y, 4 homozygous and 8 heterozygous individuals) with familial hypercholesterolemia treated by LDL-apheresis or rheohaemapheresis for 3-12 y was included in the study. In addition to cholesterol and triacylglycerol levels, vitamin E and vitamin A and also other markers of antioxidant activity were investigated. Nevertheless, the most important determined parameter was the vitamin E/cholesterol ratio in serum and lipoproteins. The results indicate that both extracorporeal elimination methods are effective and suitable ways to treat severe familial hypercholesterolemia, as the LDL fraction of cholesterol decreased by approximately 77% and 66% following LDL-apheresis and rheohaemapheresis, respectively. In addition, the serum vitamin E decreased by 54% and 57% and the decrease of the serum vitamin A was approximately 20%. However, the main marker of antioxidant capacity, vitamin E/cholesterol ratio, in the serum, VLDL and LDL significantly increased. The increase of vitamin E levels in the erythrocyte membranes of 2% following LDL-apheresis and a significant increase of 4% following rheohaemapheresis were confirmed. The presented results indicate that LDL-apheresis and rheohaemapheresis can be considered to be safe procedures according to the antioxidant capacity of the serum, VLDL and LDL lipoprotein fractions and the erythrocyte membrane.

  17. Transgenic expression of CYP7A1 in LDL receptor-deficient mice blocks diet-induced hypercholesterolemia.

    Science.gov (United States)

    Ratliff, Eric P; Gutierrez, Alejandra; Davis, Roger A

    2006-07-01

    Constitutive expression of a cholesterol-7alpha-hydroxylase (CYP7A1) transgene in LDL receptor-deficient mice blocked the ability of a cholesterol-enriched diet to increase plasma levels of apolipoprotein B-containing lipoproteins. LDL receptor-deficient mice expressing the CYP7A1 transgene exhibited complete resistance to diet-induced hypercholesterolemia and to the accumulation of cholesterol in the liver. Hepatic mRNA expression of liver X receptor-inducible ABCG5 and ABCG8 was decreased in CYP7A1 transgenic, LDL receptor-deficient mice fed a cholesterol-enriched diet. Thus, increased biliary cholesterol excretion could not account for the maintenance of cholesterol homeostasis. CYP7A1 transgenic, LDL receptor-deficient mice fed the cholesterol-enriched diet exhibited decreased jejunal Niemann-Pick C1-Like 1 protein (NPC1L1) mRNA expression, an important mediator of intestinal cholesterol absorption. A taurocholate-enriched diet also decreased NPC1L1 mRNA expression in a farnesoid X receptor-independent manner. Reduced expression of NPC1L1 mRNA was associated with decreased cholesterol absorption ( approximately 20%; P CYP7A1 transgenic LDL receptor-deficient mice fed the cholesterol-enriched diet. The combined data show that enhanced expression of CYP7A1 is an effective means to prevent the accumulation of cholesterol in the liver and of atherogenic apolipoprotein B-containing lipoproteins in plasma.

  18. A high LDL-C to HDL-C ratio predicts poor prognosis for initially metastatic colorectal cancer patients with elevations in LDL-C.

    Science.gov (United States)

    Liao, Fangxin; He, Wenzhuo; Jiang, Chang; Yin, Chenxi; Guo, Guifang; Chen, Xuxian; Qiu, Huijuan; Rong, Yuming; Zhang, Bei; Xu, Dazhi; Xia, Liangping

    2015-01-01

    Although lipid disequilibrium has been documented for several types of cancer including colorectal cancer (CRC), it remains unknown whether lipid parameters are associated with the outcome of metastatic CRC (mCRC) patients. Here, we retrospectively examined the lipid profiles of 453 mCRC patients and investigated whether any of the lipid parameters correlated with the outcome of mCRC patients. Pretreatment serum lipids, including triglyceride, cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), were collected in 453 initially mCRC patients. The LDL-C to HDL-C ratio (LHR) was calculated and divided into the first, second, and third tertiles. Univariate and multivariate analyses were performed to evaluate the impact of lipids on overall survival (OS) and progression-free survival (PFS). Nearly two-fifths of the patients (41.3%) exhibited elevations in LDL-C while most patients (88.3%) showed normal HDL-C levels. Decreased HDL-C (P=0.542) and increased LDL-C (P=0.023) were prognostic factors for poor OS, while triglyceride (P=0.542) and cholesterol (P=0.215) were not. Multivariate analysis revealed that LDL-C (P=0.031) was an independent prognostic factor. Triglyceride, cholesterol, HDL-C, and LDL-C did not correlate with PFS. Among patients with elevations in LDL-C levels, patients in the third tertile of the LHR had a markedly shorter median OS compared to those in the first or second tertile (P=0.012). Thus, increased LDL-C level is an independent prognostic factor for poor prognosis in mCRC patients, and a high LHR predicts poor prognosis for initially mCRC patients with elevations in LDL-C.

  19. About Cholesterol

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Cholesterol Updated:Apr 3,2017 It may surprise you ... our bodies to keep us healthy. What is cholesterol and where does it come from? Cholesterol is ...

  20. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the substantiation of a health claim related to a combination of Tuscan black cabbage, “tri-coloured” Swiss chard, “bicoloured” spinach and “blu savoy” cabbage and maintenance of normal blood LDL-cholesterol concentration pursuant to Article 13(5) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    related to a combination of Tuscan black cabbage, “tri-coloured” Swiss chard, “bi-coloured” spinach and “blu savoy” cabbage and maintenance of normal blood cholesterol concentration. The food that is the subject of the health claim, a combination of Tuscan black cabbage (Brassica Oleracea botrytis L.......), “tri-coloured” Swiss chard (Beta vulgaris ciclaL.), “bi-coloured” spinach (Spinacia oleracea L.) and “blu savoy” cabbage (Brassica oleracea convar. capitata var. sabauda L.), is sufficiently characterised. The claimed effect, maintenance of normal blood LDL-cholesterol concentration, is a beneficial...... physiological effect. No human intervention studies from which conclusions could be drawn for the scientific substantiation of the claim were provided by the applicant. The Panel concludes that a cause and effect relationship has not been established between consumption of a combination of Tuscan black cabbage...

  1. Cholesterol metabolism and colon cancer.

    Science.gov (United States)

    Broitman, S A; Cerda, S; Wilkinson, J

    1993-01-01

    low density lipoprotein to support cellular growth, unlike normal fibroblasts. Diminished low density lipoprotein (LDL) receptor (LDL-R) activity is a significant alteration in a metabolic pathway with such fundamental ties to cellular growth and activation (via mevalonate effects on isoprenylation of G-proteins for example), that it is selected for in the development of certain tumors--among them human colonic carcinomas. It would be expected that such a loss would provide a growth advantage to the tumor cell. Preliminary investigation of this hypothesis has shown that LDL will inhibit the proliferative capacity of certain human colonic adenocarcinomas, and that these cells possess a high rate of cholesterol synthesis relative to fibroblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

  2. Evaluating computational models of cholesterol metabolism.

    Science.gov (United States)

    Paalvast, Yared; Kuivenhoven, Jan Albert; Groen, Albert K

    2015-10-01

    Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of cholesterol synthesis and plasma cholesterol levels is incomplete. One way of addressing the remaining questions is by making use of computational models. Here, we critically evaluate existing computational models of cholesterol metabolism making use of ordinary differential equations and addressed whether they used assumptions and make predictions in line with current knowledge on cholesterol homeostasis. Having studied the results described by the authors, we have also tested their models. This was done primarily by testing the effect of statin treatment in each model. Ten out of eleven models tested have made assumptions in line with current knowledge of cholesterol metabolism. Three out of the ten remaining models made correct predictions, i.e. predicting a decrease in plasma total and LDL cholesterol or increased uptake of LDL upon treatment upon the use of statins. In conclusion, few models on cholesterol metabolism are able to pass a functional test. Apparently most models have not undergone the critical iterative systems biology cycle of validation. We expect modeling of cholesterol metabolism to go through many more model topologies and iterative cycles and welcome the increased understanding of cholesterol metabolism these are likely to bring.

  3. Intracellular transport of cholesterol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of ({sup 3}H)cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth.

  4. [LDL apheresis in the treatment of familial hypercholesterolemia].

    Science.gov (United States)

    Coker, Mahmut

    2014-10-01

    Low density lipoprotein (LDL) apheresis is one of the main therapeutic models for homozygous and severe heterozygous form of the familial hypercholesterolemia patients. Anti-atherogenic, anti-thrombogenic and anti-inflammatory effects of apheresis has positive effects on prevention of cardiovascular disease by improving of the tissue perfusion. Blood LDL cholesterol levels, response to medical therapy, presence or severity of the coronary heart disease are the main determinants of the apheresis indications. Except bleeding tendency and heparin sensitivity, there are no contraindications. In parallel with low body weight, pediatric practice could be more risky; however, there is also a 3.5-year-old apheresis application without problems. The first successful plasmapherisis for the removal of LDL cholesterol in circulation was performed in 1975. Plasmapheresis, today, is only emergency treatment model in cases of life-threatening hyperchylomicronemia. New apheresis techniques have rather high selectivity for atherogenic lipoproteins containing apolipoprotein-B100. If existing apheresis technique has low effectiveness (acute decrease of LDL cholesterol apheresis treatment significantly reduce the burden of cardiovascular disease in children and adult patients with homozygous or severe heterozygous familial hypercholesterolemia.

  5. Insulin resistance, small LDL particles, and risk for atherosclerotic disease.

    Science.gov (United States)

    Toth, Peter P

    2014-01-01

    There is a global epidemic of obesity, metabolic syndrome, and diabetes mellitus. Insulin resistance (IR) is etiologic for both metabolic syndrome and diabetes mellitus. IR induces a broad range of toxic systemic effects, including dyslipidemia, hypertension, hyperglycemia, increased production of advanced glycosylation end products, increased inflammatory tone, as well as a prothrombotic and pro-oxidative state. Patients with IR are highly vulnerable to the development of accelerated atherosclerosis as well its clinical sequelae, including coronary artery disease and myocardial infarction, carotid artery disease and ischemic stroke, peripheral arterial disease and claudication/lower extremity amputation, and coronary mortality. Among the most important risk factors patients afflicted with IR develop is the so-called atherogenic lipid triad: large numbers of small, dense low-density lipoprotein (sdLDL) particles, hypertriglyceridemia, and low serum concentrations of high-density lipoprotein cholesterol. Though controversial, much recent evidence suggests that the formation of sdLDL particles in the setting of IR is an important metabolic transition. Some studies suggest that these smaller particles are more atherogenic than their larger, more buoyant counterparts. At least part of the explanation for the apparent augmented atherogenicity of small LDL particles is their reduced systemic clearance by the LDL receptor, increased vulnerability to oxidation rendering them more apt for scavenging by macrophages, and possible increased flux into the subendothelial space of arterial walls. Numerous small studies suggest that sdLDL is highly correlated with cardiovascular events. Cardiovascular medicine is in need of a large prospective, randomized study that would more definitively investigate the impact of small, dense LDL (sdLDL) on risk for cardiovascular disease and whether therapeutic interventions designed to specifically reduce the burden of sdLDL are associated

  6. Phthalocyanine-labeled LDL for tumor imaging and photodynamic therapy

    Science.gov (United States)

    Li, Hui; Marotta, Diane; Kim, Soungkyoo; Chance, Britton; Glickson, Jerry D.; Busch, Theresa M.; Zheng, Gang

    2005-01-01

    Current limitation of both near-infrared (NIR) tumor imaging and photodynamic therapy (PDT) is their lack of sufficient tumor-to-tissue contrast due to the relatively non-specific nature of delivering dye to the tumor, which has led to false negatives for NIR imaging and inadequate therapeutic ratio for PDT. Hence, agents targeting "cancer signatures", i.e. molecules that accumulate selectively in cancer cells, are particular attractive. One of these signatures is low-density-lipoprotein receptor (LDLR), which is overexpressed in many tumors. We have developed pyropheophorbide cholesterol oleate reconstituted LDL as a LDLR-targeting photosensitizer (PS) and demonstrated its LDLR-mediated uptake in vitro and in vivo. To improve the labeling efficiency for achieving high probe/protein ratio, tetra-t-butyl silicon phthalocyanine bearing two oleate moieties at its axial positions, (tBu)4SiPcBOA, was designed and synthesized. This compound was designed to 1) prevent the PS aggregation; 2) improve the PS solubility in non-polar solvent; and 3) maximize the PS binding to LDL phospholipid monolayer. Using this novel strategy, (tBu)4SiPcBOA was reconstituted into LDL (r-SiPcBOA-LDL) with a very high payload (500:1 molar ratio). In addition, (tBu)4SiPcBOA reconstituted acetylated LDL (r-SiPcBOA)-AcLDL with similar payload was also prepared. Since Ac-LDL cannot bind to LDLR, (r-SiPcBOA)-AcLDL can serve as the negative control to evaluate LDLR targeting specificity. For biological evaluation of these new agents, confocal microscopy and in vitro PDT protocols were performed using LDLR-overexpressing human hepatoblastoma G2 (HepG2) tumor model. These studies suggest that LDL serves as a delivery vehicle to bring large amount of the NIR/PDT agents selectively to tumor cells overexpressing LDLR.

  7. The Regulating Effect of the Supplemented Wuling Powder on Total Cholesterol and LDL Cholesterol in Hyperuricemia Model Rats%加味五苓散对高尿酸血症大鼠总胆固醇及低密度脂蛋白胆固醇的调节作用

    Institute of Scientific and Technical Information of China (English)

    张玉珊; 余琼琼; 杨亚龙; 黄海

    2013-01-01

    目的:观测加味五苓散(五苓散加味萆薜、茵陈)对高尿酸血症大鼠代谢性指标总胆固醇、低密度脂蛋白胆固醇的调节作用机理方法:以腺嘌呤和盐酸乙胺丁醇混悬液灌胃,制造大鼠高尿酸血症动物模型.采取边造模边给药,加味五芩散大、中、小剂量组灌胃给药.第8、15、22d眼眶取血,分别检测总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)等指标.结果:加味五苓散中剂量组能有效降低高尿酸血症大鼠的TC、LDL-C水平(P<0.05).结论:加味五苓散具有明显降低大鼠总胆固醇、低密度脂蛋白胆固醇的作用.

  8. Antibodies against electronegative LDL inhibit atherosclerosis in LDLr-/- mice

    Directory of Open Access Journals (Sweden)

    D.M. Grosso

    2008-12-01

    Full Text Available In order to determine the effect of antibodies against electronegative low-density lipoprotein LDL(- on atherogenesis, five groups of LDL low receptor-deficient (LDLr-/- mice (6 per group were immunized with the following antibodies (100 µg each: mouse anti-LDL(- monoclonal IgG2b, rabbit anti-LDL(- polyclonal IgG or its Fab fragments and mouse irrelevant monoclonal IgG and non-immunized controls. Antibodies were administered intravenously one week before starting the hypercholesterolemic diet (1.25% cholesterol and then every week for 21 days. The passive immunization with anti-LDL(- monoclonal IgG2b, polyclonal antibody and its derived Fab significantly reduced the cross-sectional area of atherosclerotic lesions at the aortic root of LDLr-/- mice (28.8 ± 9.7, 67.3 ± 17.02, 56.9 ± 8.02 µm² (mean ± SD, respectively compared to control (124.9 ± 13.2 µm². Vascular cell adhesion molecule-1 protein expression, quantified by the KS300 image-analyzing software, on endothelium and the number of macrophages in the intima was also decreased in aortas of mice treated with anti-LDL(- monoclonal antibody (3.5 ± 0.70 per field x 10 compared to controls (21.5 ± 3.5 per field x 10. Furthermore, immunization with the monoclonal antibody decreased the concentration of LDL(- in blood plasma (immunized: 1.0 ± 1.4; control: 20.5 ± 3.5 RLU, the amount of cholesterol oxides in plasma (immunized: 4.7 ± 2.7; control: 15.0 ± 2.0 pg COx/mg cholesterol and liver (immunized: 2.3 ± 1.5; control: 30.0 ± 26.0 pg COx/mg cholesterol, and the hepatic content of lipid hydroperoxides (immunized: 0.30 ± 0.020; control: 0.38 ± 0.15 ng/mg protein. In conclusion, antibodies against electronegative LDL administered intravenously may play a protective role in atherosclerosis.

  9. ATVB Council Statement: Non-statin LDL-lowering Therapy and Cardiovascular Risk Reduction

    Science.gov (United States)

    Hegele, Robert A.; Gidding, Samuel S.; Ginsberg, Henry N.; McPherson, Ruth; Raal, Frederick J.; Rader, Daniel J.; Robinson, Jennifer G.; Welty, Francine K.

    2015-01-01

    Pharmacologic reduction of low-density lipoprotein (LDL) cholesterol using statin drugs is foundational therapy to reduce cardiovascular disease (CVD) risk. Here we consider the place of non-statin therapies that also reduce LDL cholesterol in prevention of CVD. Among conventional non-statins, placebo-controlled randomized clinical trials showed that bile acid sequestrants, niacin and fibrates given as monotherapy each reduce CVD end points. From trials in which patients’ LDL cholesterol was already well-controlled on a statin, adding ezetimibe incrementally reduced CVD end points, while adding a fibrate or niacin showed no incremental benefit. Among emerging non-statins, monoclonal antibodies against proprotein convertase subtilisin kexin type 9 (PCSK9) added to a statin and given for up to 78 weeks showed preliminary evidence of reductions in CVD outcomes. While these promising early findings contributed to the recent approval of these agents in Europe and the US, much larger and longer duration outcomes studies are ongoing for definitive proof of CVD benefits. Other non-statin agents recently approved in the US include lomitapide and mipomersen, which both act via distinctive LDL-receptor independent mechanisms to substantially reduce LDL cholesterol in homozygous familial hypercholesterolemia. We also address some unanswered questions, including measuring alternative biochemical variables to LDL cholesterol, evidence for treating children with monitoring of subclinical atherosclerosis, and potential risks of extremely low LDL cholesterol. As evidence for benefit in CVD prevention accumulates, we anticipate that clinical practice will shift towards more assertive LDL-lowering treatment, using both statins and non-statins initiated earlier in appropriately selected patients. PMID:26376908

  10. Towards increased selectivity of drug delivery to cancer cells: development of a LDL-based nanodelivery system for hydrophobic photosensitizers

    Science.gov (United States)

    Buzova, Diana; Huntosova, Veronika; Kasak, Peter; Petrovajova, Dana; Joniova, Jaroslava; Dzurova, Lenka; Nadova, Zuzana; Sureau, Franck; Midkovsky, Pavol; Jancura, Daniel

    2012-10-01

    Low-density lipoproteins (LDL), a natural in vivo carrier of cholesterol in the vascular system, play a key role in the delivery of hydrophobic photosensitizers (pts) to tumor cells in photodynamic therapy (PDT) of cancer. To make this delivery system even more efficient, we have constructed a nano-delivery system by coating of LDL surface by polyethylene glycol (PEG) and dextran. Fluorescence spectroscopy and confocal fluorescence imaging were used to characterize redistribution of hypericin (Hyp), a natural potent pts, loaded in LDL/PEG and LDL/dextran complexes to free LDL molecules as well as to monitor cellular uptake of Hyp by U87-MG cells. It was shown than the redistribution process of Hyp between LDL molecules is significantly suppressed by dextran coating of LDL surface. On the other hand, PEG does not significantly influence this process. The modification of LDL molecules by the polymers does not inhibit their recognition by cellular LDL receptors. U-87 MG cellular uptake of Hyp loaded in LDL/PEG and LDL/dextran complexes appears to be similar to that one observed for Hyp transported by unmodified LDL particles. It is proposed that by polymers modified LDL molecules could be used as a basis for construction of a drug transport system for targeted delivery of hydrophobic drugs to cancer cells expressing high level of LDL receptors.

  11. Scratching the surface: Regulation of cell surface receptors in cholesterol metabolism

    NARCIS (Netherlands)

    J.K. Nelson

    2016-01-01

    Elevated plasma levels of low density lipoprotein cholesterol (LDL) are an established risk factor for the development of atherosclerosis and cardiovascular diseases. The LDL-Receptor is a key determinant in regulating LDL levels in plasma, and current lipid-lowering strategies aim to increase its c

  12. LDL oxidada y la aterosclerosis

    Directory of Open Access Journals (Sweden)

    Carlos Carvajal Carvajal

    2015-03-01

    Full Text Available El término LDL oxidada es utilizado para describir una amplia variedad de preparaciones de LDL que han sido modificadas ex vivo bajo condiciones definidas o aisladas de fuentes biológicas. La oxidación de la partícula de LDL es un proceso complejo en el cual la proteína y los lípidos constituyentes sufren cambios oxidativos originando productos complejos. La LDL oxidada juega un papel clave en la iniciación y la progresión de la aterogénesis caracterizada por una inflamación crónica, la acumulación de lípidos y modificaciones de las células vasculares en la pared arterial. A diferencia de las LDL nativas, las LDL oxidadas no son reconocidas por los receptores de LDL y más bien son captadas en una forma no regulada por receptores scavenger en las células vasculares. Este proceso lleva a la acumulación de colesterol en la pared vascular originando las células espumosas, características de la lesión aterosclerótica. Niveles aumentados de LDL oxidada han sido demostrados en pacientes con enfermedad arterial coronaria (CAD y sugieren que el nivel plasmático de la LDL oxidada puede ser un marcador de CAD.

  13. Validity of animal models for the cholesterol-raising effects of coffee diterpenes in human subjects

    NARCIS (Netherlands)

    Roos, de B.; Sawyer, J.K.; Katan, M.B.; Rudel, L.L.

    1999-01-01

    Cafestol and kahweol, coffee lipids present in unfiltered coffee brews, potently increase LDL-cholesterol concentration in human subjects. We searched for an animal species in which cafestol similarly increases LDL-cholesterol. Such an animal model could be used subsequently as a model to study the

  14. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials

    NARCIS (Netherlands)

    Mensink, R.P.; Zock, P.L.; Kester, A.D.M.; Katan, M.B.

    2003-01-01

    Background: The effects of dietary fats on the risk of coronary artery disease (CAD) have traditionally been estimated from their effects on LDL cholesterol. Fats, however, also affect HDL cholesterol, and the ratio of total to HDL cholesterol is a more specific marker of CAD than is LDL cholesterol

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1989-05-01

    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.

  16. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  17. Sex Differences in the Impact of the Mediterranean Diet on LDL Particle Size Distribution and Oxidation

    Directory of Open Access Journals (Sweden)

    Alexandra Bédard

    2015-05-01

    Full Text Available Sex differences have been previously highlighted in the cardioprotective effects of the Mediterranean diet (MedDiet. The objective of this study was to investigate whether sex differences also exist with regard to LDL particle size distribution and oxidation. Participants were 37 men and 32 premenopausal women (24–53 years with slightly elevated LDL-C concentrations (3.4–4.9 mmol/L or total cholesterol/HDL-C ≥5.0. Variables were measured before and after a four-week isoenergetic MedDiet. Sex differences were found in response to the MedDiet for the proportion of medium LDL (255–260 Å (p for sex-by-time interaction = 0.01 and small, dense LDL (sdLDL; <255 Å (trend; p for sex-by-time interaction = 0.06, men experiencing an increase in the proportion of medium LDL with a concomitant reduction in the proportion of sdLDL, while an opposite trend was observed in women. A sex difference was also noted for estimated cholesterol concentrations among sdLDL (p for sex-by-time interaction = 0.03, with only men experiencing a reduction in response to the MedDiet. The MedDiet marginally reduced oxidized LDL (oxLDL concentrations (p = 0.07, with no sex difference. Results suggest that short-term consumption of the MedDiet leads to a favorable redistribution of LDL subclasses from smaller to larger LDL only in men. These results highlight the importance of considering sex issues in cardiovascular benefits of the MedDiet.

  18. Curcumin up-regulates LDL receptor expression via the sterol regulatory element pathway in HepG2 cells.

    Science.gov (United States)

    Dou, Xiaobing; Fan, Chunlei; Wo, Like; Yan, Jin; Qian, Ying; Wo, Xingde

    2008-09-01

    Plasma low-density lipoprotein-cholesterol (LDL-C) is mainly taken up and cleared by the hepatocellular LDL receptor (LDL-R). LDL-R gene expression is regulated by the sterol regulatory element binding proteins (SREBPs). Previous studies have shown that curcumin reduces plasma LDL-C and has hypolipidemic and anti-atherosclerotic effects. Herein, we investigated the effect of curcumin on LDL-R expression and its molecular mechanism in HepG2 cells. Curcumin increased LDL-R expression (mRNA and protein) and the resultant uptake of DiI-LDL in a dose- and time-dependent manner. Using a GFP reporter system in a transfected HepG2/SRE-GFP cell line, we found that curcumin activated the sterol regulatory element of the LDL-R promoter. In HepG2/Insig2 cells, curcumin reversed the inhibition of LDL-R expression induced by Insig2 overexpression. These data demonstrate that curcumin increases LDL-R protein expression and uptake activity via the SREBPs pathway. These findings contribute to our further understanding of the cholesterol-lowering and anti-atherosclerotic effects of curcumin.

  19. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance of such gene......To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...

  20. LDL but not HDL increases adiponectin release of primary human adipocytes.

    Science.gov (United States)

    Krautbauer, Sabrina; Neumeier, Markus; Eisinger, Kristina; Hader, Yvonne; Dada, Ashraf; Schmitz, Gerd; Aslanidis, Charalampos; Buechler, Christa

    2013-12-01

    Adipocytes in obesity have inappropriately low cholesterol while adiponectin release is reduced. Cholesterol shortage may contribute to low adiponectin and 3T3-L1 cells treated with lovastatin have diminished adiponectin in cell supernatants. LDL and HDL deliver cholesterol to adipocytes. LDL but not HDL increases adiponectin in cell supernatants of primary human adipocytes. The effect of LDL is not blocked by receptor associated protein suggesting that members of the LDL-receptor family are not involved. To evaluate whether these in vitro observations translate into changes in systemic adiponectin, adiponectin was measured in serum of three patients before, immediately after and 3d after LDL-apheresis. Whereas circulating lipoproteins are reduced immediately after apheresis adiponectin is not changed. Therefore, acute lowering of lipoproteins does not affect systemic adiponectin also excluding that plenty of adiponectin is bound to lipoprotein particles. Accordingly, levels of adiponectin in purified lipoproteins are quite low. Familial hypobetalipoproteinemia (FHBL) is a rare disorder associated with low plasma LDL. Serum adiponectin is, however, similar compared to healthy controls. Thus, neither LDL nor HDL directly contributes to circulating adiponectin concentrations.

  1. Bis(Monoacylglycero)Phosphate, oxysterols and ORP11 : a threesome regulating intracellular cholesterol traffic in macrophages

    OpenAIRE

    Arnal, Maud

    2015-01-01

    Atherosclerosis is a major cardiovascular complication in increased oxidative stress-related diseases such as type 2 diabetes and metabolic syndrome. In these situations, the low density lipoproteins (LDL) undergo oxidation and their high uptake induces cholesterol accumulation in subendothelial macrophages. On the other hand, oxidized LDL are enriched in cholesterol oxidation products called oxysterols, some of them are involved in the ability of oxidized LDL to induce cellular oxidative str...

  2. Oxidized LDL upregulated ATP binding cassette transporter-1 in THP-1 macrophages

    Institute of Scientific and Technical Information of China (English)

    Chao-ke TANG; Guang-hui YI; Jun-hao YANG; Lu-shan LIU; Zuo WANG; Chang-geng RUAN; Yong-zong YANG

    2004-01-01

    AIM: To study the effect of oxidized low density lipoprotein (ox-LDL) on ATP binding cassette transporter A1 (ABCA1) in THP-1 macrophages. METHODS: After exposing the cultured THP-1 macrophages to ox-LDL for different periods, cholesterol efflux was determined by FJ-2107P type liquid scintillator. ABCA1 mRNA and protein level were determined by reverse trancriptase-polymerase chain reaction (RT-PCR) and Western blot, respectively.The cholesterol level in THP-1 macrophage foam cells was detected by high performance liquid chromatography.RESULTS: ox-LDL elevated AB CA1 in both protein and mRNA levels and increased apolipoprotein (apo) A-I-mediated cholesterol efflux in a time- and dose-dependent manner. 22(R)-hydroxyeholesterol and 9-cis-retinoic acid did significantly increase cholesterol efflux in THP-1 macrophage foam cells (P<0.05), respectively. Both of them further promoted cholesterol efflux (P<0.01). As expected, liver X receptor (LXR) agonist decreased content of esterified cholesterol in the macrophage foam cells compared with control, whereas only a slight decrease of free cholesterol was observed. LXR activity was slightly increased by oxidized LDL by 12 % at 12 h compared with 6 h.However, LXR activity was increased about 1.8 times at 24 h, and oxidized LDL further increased LXR activity by about 2.6 times at 48 h. CONCLUSION: ABCA1 gene expression was markedly increased in cholesterol-loaded cells as a result of activation of LXR/RXR. ABCA1 plays an important role in the homeostasis of cholesterol in the macrophages.

  3. LDL electronegativity index: a potential novel index for predicting cardiovascular disease

    Directory of Open Access Journals (Sweden)

    Ivanova EA

    2015-08-01

    Full Text Available Ekaterina A Ivanova,1 Yuri V Bobryshev,2,3 Alexander N Orekhov2,4,5 1Department of Pediatric Nephrology and Growth and Regeneration, Katholieke Universiteit Leuven and University Hospitals Leuven, Leuven, Belgium; 2Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, Russian Academy of Sciences, Moscow, Russia; 3Faculty of Medicine, School of Medical Sciences, University of New South Wales, Kensington, Sydney, NSW, Australia; 4Institute for Atherosclerosis Research, Skolkovo Innovative Center, Moscow, Russia; 5Department of Biophysics, Faculty of Biology, Lomonosov Moscow State University, Moscow, Russia Abstract: High cardiovascular risk conditions are frequently associated with altered plasma lipoprotein profile, such as elevated low-density lipoprotein (LDL and LDL cholesterol and decreased high-density lipoprotein. There is, however, accumulating evidence that specific subclasses of LDL may play an important role in cardiovascular disease development, and their relative concentration can be regarded as a more relevant risk factor. LDL particles undergo multiple modifications in plasma that can lead to the increase of their negative charge. The resulting electronegative LDL [LDL(−] subfraction has been demonstrated to be especially atherogenic, and became a subject of numerous recent studies. In this review, we discuss the physicochemical properties of LDL(−, methods of its detection, atherogenic activity, and relevance of the LDL electronegativity index as a potential independent predictor of cardiovascular risk. Keywords: low-density lipoprotein, LDL, LDL electronegativity index, cardiovascular disease, atherosclerosis

  4. [Cholesterol and atherosclerosis. Historical considerations and treatment].

    Science.gov (United States)

    Zárate, Arturo; Manuel-Apolinar, Leticia; Basurto, Lourdes; De la Chesnaye, Elsa; Saldívar, Iván

    2016-01-01

    Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming «cholesterol»; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

  5. 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

  6. Mechanism of Resistance to Dietary Cholesterol

    Directory of Open Access Journals (Sweden)

    Lindsey R. Boone

    2011-01-01

    Full Text Available Background. Alterations in expression of hepatic genes that could contribute to resistance to dietary cholesterol were investigated in Sprague-Dawley rats, which are known to be resistant to the serum cholesterol raising action of dietary cholesterol. Methods. Microarray analysis was used to provide a comprehensive analysis of changes in hepatic gene expression in rats in response to dietary cholesterol. Changes were confirmed by RT-PCR analysis. Western blotting was employed to measure changes in hepatic cholesterol 7α hydroxylase protein. Results. Of the 28,000 genes examined using the Affymetrix rat microarray, relatively few were significantly altered. As expected, decreases were observed for several genes that encode enzymes of the cholesterol biosynthetic pathway. The largest decreases were seen for squalene epoxidase and lanosterol 14α demethylase (CYP 51A1. These changes were confirmed by quantitative RT-PCR. LDL receptor expression was not altered by dietary cholesterol. Critically, the expression of cholesterol 7α hydroxylase, which catalyzes the rate-limiting step in bile acid synthesis, was increased over 4-fold in livers of rats fed diets containing 1% cholesterol. In contrast, mice, which are not resistant to dietary cholesterol, exhibited lower hepatic cholesterol 7α hydroxylase (CYP7A1 protein levels, which were not increased in response to diets containing 2% cholesterol.

  7. Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the golden Syrian hamster.

    Science.gov (United States)

    Burke, Katie T; Colvin, Perry L; Myatt, Leslie; Graf, Gregory A; Schroeder, Friedhelm; Woollett, Laura A

    2009-06-01

    The fetus has a high requirement for cholesterol and synthesizes cholesterol at elevated rates. Recent studies suggest that fetal cholesterol also can be obtained from exogenous sources. The purpose of the current study was to examine the transport of maternal cholesterol to the fetus and determine the mechanism responsible for any cholesterol-driven changes in transport. Studies were completed in pregnant hamsters with normal and elevated plasma cholesterol concentrations. Cholesterol feeding resulted in a 3.1-fold increase in the amount of LDL-cholesterol taken up by the fetus and a 2.4-fold increase in the amount of HDL-cholesterol taken up. LDL-cholesterol was transported to the fetus primarily by the placenta, and HDL-cholesterol was transported by the yolk sac and placenta. Several proteins associated with sterol transport and efflux, including those induced by activated liver X receptor, were expressed in hamster and human placentas: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas. Thus, increasing maternal lipoprotein-cholesterol concentrations can enhance transport of maternal cholesterol to the fetus, leading to 1) increased movement of cholesterol down a concentration gradient in the placenta, 2) increased lipoprotein secretion from the yolk sac (shown previously), and possibly 3) increased placental NPC1L1 expression.

  8. Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect.

    Directory of Open Access Journals (Sweden)

    Gerd Hörl

    Full Text Available We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC. LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high-performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation were investigated in 11 patients with confirmed coronary artery disease (CAD. We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL-IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL-apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known

  9. Synthetic LDL as targeted drug delivery vehicle

    Science.gov (United States)

    Forte, Trudy M.; Nikanjam, Mina

    2012-08-28

    The present invention provides a synthetic LDL nanoparticle comprising a lipid moiety and a synthetic chimeric peptide so as to be capable of binding the LDL receptor. The synthetic LDL nanoparticle of the present invention is capable of incorporating and targeting therapeutics to cells expressing the LDL receptor for diseases associated with the expression of the LDL receptor such as central nervous system diseases. The invention further provides methods of using such synthetic LDL nanoparticles.

  10. High Blood Cholesterol

    Science.gov (United States)

    ... version of this page please turn Javascript on. High Blood Cholesterol What is High Blood Cholesterol? What is Cholesterol? Cholesterol is a ... heart disease. If Your Blood Cholesterol Is Too High Too much cholesterol in your blood is called ...

  11. Does fat in milk, butter and and cholesterol differently?

    DEFF Research Database (Denmark)

    Tholstrup, T,; Høy, Carl-Erik; Andersen, L.N.

    2004-01-01

    and 8 hours following intake of the meals. Results: Fasting LDL cholesterol concentration was significantly higher after butter than cheese diet (p 0.037), with a borderline significant difference in total cholesterol (p = 0.054) after the experimental periods of three weeks. Postprandial glucose showed...... a higher response after cheese diet than after milk diet (p = 0.010, diet X time interaction). Conclusions: A different effect of fat in milk and butter could not be confirmed in this study. The moderately lower LDL cholesterol after cheese diet compared to butter diet should be investigated further....

  12. Genetic determinants of LDL, lipoprotein(a), triglyceride-rich lipoproteins and HDL: concordance and discordance with cardiovascular disease risk

    DEFF Research Database (Denmark)

    Nordestgaard, Børge G; Tybjærg-Hansen, Anne

    2011-01-01

    To evaluate whether new and known genetic determinants of plasma levels of LDL cholesterol, lipoprotein(a), triglyceride-rich lipoproteins, and HDL cholesterol associate with the risk of cardiovascular disease expected from the effect on lipoprotein levels. Concordance or discordance...... of such genetic determinants with cardiovascular disease risk will either favor or disfavor that these lipoproteins are causally related to cardiovascular disease....

  13. 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...

  14. [Prostate cancer dependance upon cholesterol, statins and diet].

    Science.gov (United States)

    Pilch, Paweł; Radziszewski, Piotr; Maciukiewicz, Piotr

    2012-01-01

    The aim of the work is to analyze the influence of higher cholesterol and LDL level on risk of prostate cancer. The work is based on the available literature in that field. The metabolism of cholesterol is mainly regulated by the statins, which may thus inhibit prostate cancer growth. Keeping the appropriate body mass and level of cholesterol by proper diet and physical exercises may be the prophylaxis of prostate cancer.

  15. Yoghurt kedelai hitam (black soyghurt dapat menurunkan kadar LDL tikus hiperkolesterolemia

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    Slamet Riyanto

    2016-08-01

    Full Text Available ABSTRACTBackground: Hypercholesterolemia is a main risk factor of cardiovascular disease that remains the higher cause of deaths in the world. Black soy bean containing protein, fiber, vitamin, isoflavon, and flavonoid can decrease serum cholesterol level. Yoghurt contains lactic acid bacteria that decrease total and LDL cholesterol, triglyceride, and increase the HDL cholesterol. Processing of black soy bean into black soyghurt can increase its isoflavon’s activity by forming aglicone, which has higher activity to decrease cholesterol.Objectives: To know the effect of black soyghurt feeding to LDL, HDL, and HDL ratio of hypercholesterolemic rats.Methods: This research was true-experimental using post test only with control group design. Subjects were 20 male Sprague dawley rats, 2 months old, inducted hypercholesterolemia, given black soyghurt diet using 2 mL, 3 mL, and 4 mL dosage for 21 days. Serum lipid profile were measured by CHOD-PAPand GPO-PAP methods respectively. Normality of the data were tested by Shapiro Wilks test. Data were analyzed by paired t test and Anova continued by LSD test using computer program.Results: The study revealed that black soyghurt 4 mL/day decreased LDL (p=0.02 at the most significant level. The other doses did not significantly influence the levels of LDL (p>0.05 . There was also no effect of black soyghurt feeding on serum HDL cholesterol levels (p=0.11 and the ratio of LDL /HDL (p=0.087.Conclusions: The feeding of black soyghurt at the dosage of 4 mL/day to hypercholesterolemic rats could decrease the serum LDL, but could decrease the ratio of LDL / HDL significantly.KEYWORDS: black soyghurt, LDL/HDL ratio, hypercholesterolemicABSTRAKLatar belakang: Hiperkolesterolemia merupakan faktor risiko penyakit kardiovaskuler yang menjadi penyebab kematian utama di dunia. Kedelai hitam mengandung protein, vitamin, serat, isoflavon, dan flavonoid yang mampu menurunkan kadar kolesterol. Yoghurt

  16. Electronegative LDL: A Circulating Modified LDL with a Role in Inflammation

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    Montserrat Estruch

    2013-01-01

    Full Text Available Electronegative low density lipoprotein (LDL(− is a minor modified fraction of LDL found in blood. It comprises a heterogeneous population of LDL particles modified by various mechanisms sharing as a common feature increased electronegativity. Modification by oxidation is one of these mechanisms. LDL(− has inflammatory properties similar to those of oxidized LDL (oxLDL, such as inflammatory cytokine release in leukocytes and endothelial cells. However, in contrast with oxLDL, LDL(− also has some anti-inflammatory effects on cultured cells. The inflammatory and anti-inflammatory properties ascribed to LDL(− suggest that it could have a dual biological effect.

  17. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  18. Liquid fructose supplementation in LDL-R−/− mice fed a western-type diet enhances lipid burden and atherosclerosis despite identical calorie consumption

    Directory of Open Access Journals (Sweden)

    Natalia Hutter

    2015-12-01

    Conclusions: SLF, without changing total calorie intake, increases atherosclerosis, visceral adipose tissue and cholesterol burden in a background of overweight LDL receptor knockout mice consuming an unhealthy, Western-type solid rodent chow.

  19. Mathematically modelling the dynamics of cholesterol metabolism and ageing.

    Science.gov (United States)

    Morgan, A E; Mooney, K M; Wilkinson, S J; Pickles, N A; Mc Auley, M T

    2016-07-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the UK. This condition becomes increasingly prevalent during ageing; 34.1% and 29.8% of males and females respectively, over 75 years of age have an underlying cardiovascular problem. The dysregulation of cholesterol metabolism is inextricably correlated with cardiovascular health and for this reason low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) are routinely used as biomarkers of CVD risk. The aim of this work was to use mathematical modelling to explore how cholesterol metabolism is affected by the ageing process. To do this we updated a previously published whole-body mathematical model of cholesterol metabolism to include an additional 96 mechanisms that are fundamental to this biological system. Additional mechanisms were added to cholesterol absorption, cholesterol synthesis, reverse cholesterol transport (RCT), bile acid synthesis, and their enterohepatic circulation. The sensitivity of the model was explored by the use of both local and global parameter scans. In addition, acute cholesterol feeding was used to explore the effectiveness of the regulatory mechanisms which are responsible for maintaining whole-body cholesterol balance. It was found that our model behaves as a hypo-responder to cholesterol feeding, while both the hepatic and intestinal pools of cholesterol increased significantly. The model was also used to explore the effects of ageing in tandem with three different cholesterol ester transfer protein (CETP) genotypes. Ageing in the presence of an atheroprotective CETP genotype, conferring low CETP activity, resulted in a 0.6% increase in LDL-C. In comparison, ageing with a genotype reflective of high CETP activity, resulted in a 1.6% increase in LDL-C. Thus, the model has illustrated the importance of CETP genotypes such as I405V, and their potential role in healthy ageing.

  20. Novel mechanism by which probucol lowers low density lipoprotein levels demonstrated in the LDL receptor-deficient rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Naruszewicz, M.; Carew, T.E.; Pittman, R.C.; Witztum, J.L.; Steinberg, D.

    1984-11-01

    Treatment of low density lipoprotein (LDL) receptor-deficient rabbits (WHHL rabbits) with probucol (1% w/w in a chow diet) lowered their LDL-cholesterol levels by 36%, consonant with the reported effectiveness of the drug in patients deficient in the LDL receptor. Initial studies of LDL fractional catabolic rate (FCR) using /sup 125/I-labeled LDL prepared from the serum of untreated WHHL rabbits showed no difference between probucol-treated WHHL rabbits and untreated WHHL rabbits. When, however, /sup 125/I-labeled LDL was prepared from donor WHHL rabbits under treatment with probucol and injected back into them, the FCR was found to be increased by about 50% above that measured simultaneously using /sup 131/I-labeled LDL prepared from untreated WHHL donors. The labeled LDL from probucol-treated donors was also metabolized more rapidly than that from untreated donors when injected into untreated WHHL rabbits or into untreated wild-type New Zealand White rabbits. Finally, it was shown that rabbit skin fibroblasts in culture degraded labeled LDL prepared from probucol-treated WHHL rabbits more rapidly than that prepared from untreated WHHL donors. This was true both for normal rabbit fibroblasts and also for WHHL skin fibroblasts, although the absolute degradation rates in the latter were, of course, much lower for both forms of LDL. The data indicate that a major mechanism by which probucol lowers LDL levels relates not to changes in the cellular mechanisms for LDL uptake or to changes in LDL production but rather to intrinsic changes in the structure and metabolism of the plasma LDL of the probucol-treated animal.

  1. Influence of infant and juvenile diets on serum cholesterol, lipoprotein cholesterol, and apolipoprotein concentrations in juvenile baboons (Papio sp.).

    Science.gov (United States)

    Mott, G E; McMahan, C A; Kelley, J L; Farley, C M; McGill, H C

    1982-11-01

    The long-term effects of infant diet (breast milk or formula containing 2, 30, or 60 mg/dl cholesterol) and subsequent dietary cholesterol (1 mg/kcal) and fat (saturated or unsaturated) on serum lipid and apolipoprotein concentrations were estimated using 82 juvenile baboons 4-6 years of age. A significant interaction of infant diet (breast vs formula) with type of fat (saturated vs unsaturated) at 4-6 years of age was observed on HDL cholesterol and apolipoprotein A-I (apoA-I) concentrations. That is, animals breast-fed as infants had higher HDL cholesterol and apoA-I concentrations when fed unsaturated fat from weaning to 4-6 years of age than those fed saturated fat (77 vs 68 mg/dl). In contrast, animals fed formulas in infancy followed by a diet containing unsaturated fat had lower HDL cholesterol and apoA-I concentrations at 4-6 years of age than did those fed saturated fat (67 vs 78 mg/dl). However, breast feeding or feeding formulas containing various levels of cholesterol for 3 months during infancy did not result in statistically significant differences in total serum cholesterol, VLDL + LDL cholesterol and apolipoprotein B (apoB) concentrations. Dietary cholesterol after infancy significantly increased serum total cholesterol, VLDL + LDL and HDL cholesterol, apoA-I and apoB concentrations. All of these response variables also were higher in animals fed saturated fat compared to those fed unsaturated fat on the same level of cholesterol. At 4-6 years of age, regardless of diet, females had significantly higher serum VLDL + LDL cholesterol (57 vs 43 mg/dl) and apoB concentrations (39 vs 30 mg/dl) than did males.

  2. Presence of elevated non-HDL among patients with T2DM with CV events despite of optimal LDL-C - A report from South India.

    Science.gov (United States)

    Kumpatla, Satyavani; Soni, Anju; Narasingan, S N; Viswanathan, Vijay

    2016-01-01

    Elevated non-high density lipoprotein cholesterol (non-HDL-C) was the commonest lipid abnormality among T2DM patients with cardiovascular events (CV) events. Prevalence of elevated non-HDL-C was 21.6% among patients who were on statin therapy and with optimal low density lipoprotein-cholesterol (LDL-C) levels. Despite an optimal LDL-C level, 47% of the T2DM patients with CV events had elevated non-HDL-C.

  3. The first results demonstrating efficiency and safety of a double-column whole blood method of LDL-apheresis.

    Science.gov (United States)

    Hequet, O; Le, Q H; Rigal, D; Mekhloufi, F; Jaeger, S; Sassolas, A; Groisne, L; Moulin, P

    2010-02-01

    LDL-apheresis is a treatment for familial hypercholesterolemia in addition to diet and drug therapy. In the past, LDL-apheresis techniques consisted in separating plasma from blood and adsorbing plasma LDL-C whereas recent methods remove LDL-C directly from whole blood. The whole blood system developed by Kaneka consists of a single-column (Liposorber DL-75) treatment (SCWB) but a double-column whole blood (DCWB) method has recently been developed (Liposorber DL-50 x 2). When 1.6 blood volumes (plus 1l) were processed, acute reductions of total cholesterol and LDL-C were 67.9+/-6% and 80.2+/-4.5%, respectively. The performances of the DCWB method were compared to other LDL-apheresis methods. Assessed in 10 patients, the DCWB method is more efficient than the SCWB method with higher reduction rates of LDL-C (79.7+/-4.9 vs. 68.2+/-5.0% papheresis method consisting of preliminary plasma separation followed by plasma LDL-C adsorption and used as first line apheresis therapy (80.5+/-4.5 vs. 79.0+/-5.9%). The safety of DCWB was demonstrated in 12 patients with only a low frequency of mild and transient adverse effects (4%). In conclusion, the DCWB LDL-apheresis method provides efficient removal of LDL-C, a low level of adverse effects, and a shortened duration of the procedure.

  4. Proportion of oxidized LDL relative to plasma apolipoprotein B does not change during statin therapy in patients with heterozygous familial hypercholesterolemia.

    NARCIS (Netherlands)

    Tits, L.J.H. van; Himbergen, T. van; Lemmers, H.L.M.; Graaf, J. de; Stalenhoef, A.F.H.

    2006-01-01

    OBJECTIVE: Circulating oxidized low-density lipoprotein (LDL) has been shown to be a useful marker for identifying patients with coronary heart disease (CHD) and persons at high cardiovascular risk. The effect of cholesterol-lowering therapy on plasma level of oxidized LDL is not clear. METHODS AND

  5. 17 beta-estradiol but not the phytoestrogen naringenin attenuates aortic cholesterol accumulation in WHHL rabbits

    DEFF Research Database (Denmark)

    Mortensen, Alicja; Breinholt, V.; Dalsgaard, T.;

    2001-01-01

    .20% naringenin, for 16 weeks. The uterine weight was increased (P cholesterol and triglycerides were not different from those in the controls, In lipoproteins, HDL...... cholesterol was increased (P cholesterol accumulation was decreased (P ... but the ratio of intima to media and area of intima in ascending, thoracic, and abdominal aorta were not significantly different. In the naringenin group the only differences, compared with the control group, were increased LDL cholesterol (P

  6. Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

    Science.gov (United States)

    Alonso, L; Fontecha, J; Cuesta, P

    2016-01-14

    A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (Pacidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD and L. acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations.

  7. Calculation of LDL apoB

    NARCIS (Netherlands)

    Sniderman, A.D.; Tremblay, A.J.; Graaf, J. de; Couture, P.

    2014-01-01

    OBJECTIVES: This study tests the validity of the Hattori formula to calculate LDL apoB based on plasma lipids and total apoB. METHODS: In 2178 patients in a tertiary care lipid clinic, LDL apoB calculated as suggested by Hattori et al. was compared to directly measured LDL apoB isolated by ultracent

  8. Effect of monounsaturated fatty acids on high-density and low-density lipoprotein cholesterol levels and blood pressure in healthy men and women.

    NARCIS (Netherlands)

    Mensink, R.P.

    1990-01-01

    The purpose of the studies described in this thesis was to examine the effect of monounsaturated fatty acids on the distribution of serum cholesterol over high-density and low-density lipoproteins (HDL and LDL) and on blood pressure in healthy men and women. High levels of LDL cholesterol and bl

  9. 新疆维吾尔族空腹血糖受损人群血脂水平变化及低密度脂蛋白胆固醇升高的相关因素分析%Risk factors related to high LDL cholesterol and abnormal lipid levels of patients with impaired fasting glucose in Xinjiang Uygur

    Institute of Scientific and Technical Information of China (English)

    胡琳; 娜丽玛; 蒋升

    2014-01-01

    目的 分析新疆维吾尔族(下称“维族”)IFG人群血脂代谢状况及LDL-C升高的危险因素. 方法 对新疆地区2053名30~80岁维族居民行横断面调查,筛查IFG人群,分析血脂代谢状况及LDL-C相关危险因素. 结果 该IFG人群中,血脂代谢异常的总患病率为99.8%(613/614).高TG血症患病率为85.5%(525/614);高TC血症、高LDL-C血症患病率分别为72.5%(445/614)和40.7%(250/614),男性均高于女性(75.0%vs70.1%,52.4%vs29.9%,P<0.05);低HDL-C血症患病率为29.8%(183/614),男性低于女性(28.0%vs31.4%,P<0.05).Logistic回归分析显示,LDL-C升高的危险因素为年龄、TC及2 hPG. 结论 维族IFG人群血脂代谢异常的总患病率为99.8%,其中高LDL-C血症的患病率为40.7%,其危险因素为年龄、TC及2 hPG.

  10. 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.

  11. Flow-mediated vasodilation is not impaired when HDL-cholesterol is lowered by substituting carbohydrates for monounsaturated fat

    NARCIS (Netherlands)

    de Roos, NM; Bots, ML; Siebelink, E; Katan, MB

    2001-01-01

    Low-fat diets, in which carbohydrates replace some of the fat, decrease serum cholesterol. This decrease is due to decreases in LDL-cholesterol but in part to possibly harmful decreases in HDL-cholesterol. High-oil diets, in which oils rich in monounsaturated fat replace some of the saturated fat, d

  12. Efficacy and safety of a new cholesterol synthesis inhibitor, atorvastatin, in comparison with simvastatin and pravastatin, in subjects with hypercholesterolemia

    NARCIS (Netherlands)

    Wolffenbuttel, B H; Mahla, G; Muller, D; Pentrup, A; Black, D M

    1998-01-01

    BACKGROUND: High levels of total and LDL-cholesterol are associated with an increased risk of atherosclerotic vascular disease. Lowering of serum cholesterol levels by pharmacologic intervention with inhibitors of cholesterol synthesis, the so-called statins, reduces the incidence of cardiovascular

  13. Effects of cholesterol and lipoproteins on endocytosis by a monocyte-like cell line.

    Science.gov (United States)

    Esfahani, M; Scerbo, L; Lund-Katz, S; DePace, D M; Maniglia, R; Alexander, J K; Phillips, M C

    1986-12-19

    The human monocyte/macrophage-like cell line U937 is a cholesterol auxotroph. Incubation of these cells in the growth medium in which delipidated fetal calf serum has been substituted for fetal calf serum depletes cellular cholesterol and inhibits growth. The cholesterol requirement of these cells for growth can be satisfied by human low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL), but not by high-density lipoprotein (HDL). U937 cells can bind and degrade LDL via a high-affinity site and this recognition is altered by acetylation of LDL. This indicates that these cells express relatively high LDL receptor activity and low levels of the acetyl-LDL receptor. The cells were used to study the role of cholesterol in lectin-mediated and fluid-phase endocytosis. Growth of the cells in the medium containing delipidated fetal calf serum results in impairment of both concanavalin A-mediated endocytosis of horseradish peroxidase and concanavalin A-independent endocytosis of Lucifer Yellow. Supplementation of the medium with cholesterol prevents cellular cholesterol depletion, supports growth and stimulates Lucifer Yellow endocytosis but fails to restore horseradish peroxidase endocytosis. However, if the cells are incubated in the presence of no less than 40 micrograms LDL protein/ml to maintain normal cell cholesterol levels, concanavalin A-mediated endocytosis of horseradish peroxidase is activated. The effect of LDL is specific since neither VLDL nor HDL3 at the same protein concentration activates horseradish peroxidase uptake by the cells. Furthermore, the activation of endocytosis by LDL is not inhibited by the inclusion of heparin or acetylation of the LDL indicating that binding of LDL to the LDL receptor is not required for these effects. The mediation of activation of horseradish peroxidase endocytosis by the lectin is presumed to involve binding of LDL to concanavalin A associated with the cell surface which in turn stimulates horseradish

  14. LDL cholesterolemia as a novel risk factor for radiographic progression of rheumatoid arthritis: a single-center prospective study.

    Directory of Open Access Journals (Sweden)

    Yune-Jung Park

    Full Text Available Dyslipidemia has been implicated in various musculoskeletal diseases, including rheumatoid arthritis (RA. Evidence is emerging that there might be a pathogenic interaction among inflammation, dyslipidemia, and adipokines. We prospectively investigated the association of cumulative lipid levels with radiographic progression of RA. RA patients (n=242 underwent plasma cholesterol assessment at four visits. Disease activity parameters and X-rays of the hands and feet were also serially monitored in these patients. The cumulative inflammatory burden and lipid levels were estimated by time-integrated values. Serum leptin and adiponectin concentrations were determined by ELISA. When patients were divided into three groups according to time-integrated lipid levels, as expected, patients with LDL cholesterol and/or triglyceride levels in the third tertile had persistently higher ESR and CRP levels. In parallel, a more rapid radiographic progression over two years was observed in patients with higher LDL cholesterol and/or triglyceride levels. In multivariate analysis, time-integrated LDL cholesterol was independently associated with radiographic progression. Particularly, the risk of radiographic progression was 5.6-fold in a subgroup with both LDL cholesterol and triglyceride levels in the third tertile. Moreover, LDL cholesterol synergistically increased the adjusted probability of radiographic progression in patients with high serum leptin levels but not in those without. These results demonstrate that LDL cholesterolemia is a novel serum marker that can be used to predict radiographic progression of RA, which seems to be related to circulatory leptin levels. We suggest that personalized and more aggressive anti-rheumatic therapy is required for dyslipidemic subgroups in RA patients.

  15. Genetic and metabolic influences on LDL subclasses

    Energy Technology Data Exchange (ETDEWEB)

    Krauss, R.M. [Lawrence Berkeley Lab., CA (United States); Rotter, J.I.; Lusis, A.J. [Univ. of California, Los Angeles, CA (United States)

    1994-09-01

    Genetic and environmental factors influence LDL particle size and density, and expression of an atherogenic lipoprotein phenotype (ALP) characterized by predominance of small, dense LDL particles. Linkage of ALP the LDL receptor locus has been reported previously. Quantitative sib-pair relative-pair linkage methodologies were used to test for linkage of LDL particle size to candidate loci in 25 large pedigrees with familial coronary artery disease. Linkage to the LDL receptor gene locus was confirmed (p=0.008). Evidence was also obtained for linkage to the genes for apoCIII, cholesteryl ester transfer protein, and manganese superoxide dismutase. The results suggest multiple genetic determinants of LDL particle size that may involve different metabolic mechanisms giving rise to small, dense LDL and increased atherosclerosis risk.

  16. Women and Cholesterol

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Women and Cholesterol Updated:Apr 1,2016 The female sex hormone ... 2014. Related Sites Nutrition Center My Life Check Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  17. Cholesterol IQ Quiz

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Feb 2,2015 Begin the quiz Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  18. Cholesterol and Your Child

    Science.gov (United States)

    ... Old Feeding Your 1- to 2-Year-Old Cholesterol and Your Child KidsHealth > For Parents > Cholesterol and ... child's risk of developing heart disease later. About Cholesterol Cholesterol is a waxy substance produced by the ...

  19. Lifestyle Changes and Cholesterol

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    ... Venous Thromboembolism Aortic Aneurysm More Lifestyle Changes and Cholesterol Updated:Sep 26,2016 As part of a ... to the Terms and Conditions and Privacy Policy Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  20. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Apr 3,2017 Cholesterol can be both ... misconceptions about cholesterol. Click on each misconception about cholesterol to see the truth: My choices about diet ...

  1. Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Frikke-Schmidt, Ruth

    2015-01-01

    AIMS: Ezetimibe reduces plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting Niemann-Pick C1-Like protein 1 (NPC1L1), the transporter responsible for cholesterol uptake from the intestine into enterocytes and from the bile into hepatocytes. We tested the hypothesis that genetic...... developed IVD or symptomatic gallstone disease, respectively, during follow-up from 1977 to 2013. We genotyped four common NPC1L1 variants, previously associated with reduced LDL cholesterol levels, thus mimicking the effect of ezetimibe, and calculated a weighted genotype score. With increasing genotype...... score, LDL cholesterol decreased stepwise up to 3.5% (0.12 mmol/L) and total cholesterol up to 1.9% (0.11 mmol/L) (P-trend: 2 × 10(-12) and 2 × 10(-9)). The cumulative incidence by age of IVD decreased, while that of symptomatic gallstone disease increased as a function of increasing genotype score (P...

  2. Oxidative modification and poor protective activity of HDL on LDL oxidation in thalassemia.

    Science.gov (United States)

    Unchern, Supeenun; Laohareungpanya, Narumon; Sanvarinda, Yupin; Pattanapanyasat, Kovit; Tanratana, Pansakorn; Chantharaksri, Udom; Sibmooh, Nathawut

    2010-07-01

    Oxidative modification of low-density lipoprotein (LDL) has been reported in thalassemia, which is a consequence of oxidative stress. However, the levels of oxidized high-density lipoprotein (HDL) in thalassemia have not been evaluated and it is unclear whether HDL oxidation may be linked to LDL oxidation. In this study, the levels of total cholesterol, iron, protein, conjugated diene (CD), lipid hydroperoxide (LOOH), and thiobarbituric acid reactive substances (TBARs) were determined in HDL from healthy volunteers and patients with beta-thalassemia intermedia with hemoglobin E (beta-thal/Hb E). The protective activity of thalassemic HDL on LDL oxidation was also investigated. The iron content of HDL(2) and HDL(3) from beta-thal/HbE patients was higher while the cholesterol content was lower than those in healthy volunteers. Thalassemic HDL(2) and HDL(3) had increased levels of lipid peroxidation markers i.e., conjugated diene, LOOH, and TBARs. Thalassemic HDL had lower peroxidase activity than control HDL and was unable to protect LDL from oxidation induced by CuSO(4). Our findings highlight the oxidative modification and poor protective activity of thalassemic HDL on LDL oxidation which may contribute to cardiovascular complications in thalassemia.

  3. Comparison of the effect of two HMG CoA reductase inhibitors on LDL susceptibility to oxidation

    Directory of Open Access Journals (Sweden)

    Vera Lúcia Portal

    2003-02-01

    Full Text Available OBJECTIVE: To study the differences between fluvastatin and pravastatin regarding LDL susceptibility to oxidation, plasma levels of total cholesterol (TC, HDL-C, LDL-C and triglycerides (TG in hypercholesterolemic patients with established coronary heart disease (CHD. METHODS: A double-blind randomized parallel study was conducted that included 41 hypercholesterolemic outpatients with CHD treated at the Instituto de Cardiologia do Rio Grande do Sul. The inclusion criteria were LDL-C above 100 mg/dL and triglycerides below 400 mg/dL based on 2 measures. After 4 weeks on a low cholesterol diet, those patients that fullfilled the inclusion criteria were randomized into 2 groups: the fluvastatin group (fluvastatin 40 mg/day and the pravastatin group (pravastatin 20 mg/day, for 24 weeks of treatment. LDL susceptibility to oxidation was analyzed with copper-induced production of conjugated dienes (Cu2+ and water-soluble free radical initiator azo-bis (2'-2'amidinopropanil HCl (AAPH. Spectroscopy nuclear magnetic resonance was used for determination of lipids. RESULTS: After 24 weeks of drug therapy, fluvastatin and pravastatin significantly reduced LDL susceptibility to oxidation as demonstrated by the reduced rate of oxidation (azo and Cu and by prolonged azo-induced lag time (azo lag. The TC, LDL-C, and TG reduced significantly and HDL-C increased significantly. No differences between the drugs were observed. CONCLUSION: In hypercholesterolemic patients with CHD, both fluvastatin and pravastatin reduced LDL susceptibility to oxidation.

  4. 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

  5. Dietary palmitic acid influences LDL-mediated lymphocyte proliferation differently to other mono- and polyunsaturated fatty acids in rats.

    Science.gov (United States)

    Tinahones, F J; Gómez-Zumaquero, J M; Monzón, A; Rojo-Martínez, G; Pareja, A; Morcillo, S; Cardona, F; Olveira, G; Soriguer, F

    2004-10-01

    Recent studies suggest that the biological effects of saturated fatty acids depend on the length of their chain. We compared the effect of diets containing different fatty acids on plasma lipids and lymphocyte proliferation in the presence of lovastatin and with increasing amounts of LDL. Lymphocytes from rats fed with a diet rich in palmitic acid had a greater lymphocyte proliferation capacity than those from rats fed with diets rich in oleic acid, linoleic acid, or fish oil. This effect was maintained when small amounts of polyunsaturatwed fatty acids (PUFA; sunflower oil) were added to the palmitic acid diet. LDL receptor activity, measured by the capacity of lovastatin to revert the inhibition of lymphocyte proliferation with increasing amounts of LDL in the medium, was greater in the rats fed with palmitic acid, and was similar to the other groups when small amounts of PUFA were added. All the groups had similar levels of plasma cholesterol, but the LDL levels were significantly lower in the group fed with palmitic acid plus PUFA. The highest HDL-cholesterol (HDLc) levels were found in the palmitic acid group and the lowest LDL-cholesterol (LDLc)/HDLc ratio in the palmitic acid plus PUFA group. These results suggest that diets rich in palmitic acid do not raise total cholesterol, but reduce LDLc or keep it normal, and raise HDLc levels. This effect may be partly due to an increase in LDL receptor activity. The inclusion of small amounts of PUFA in the diet rich in palmitic acid substantially modified the LDL receptor response in the lymphocytes, suggesting that the proportion of different families of dietary fatty acids may be more important than the individual amount of each in absolute terms to explain their effects on plasma lipids and lipoproteins.

  6. The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model.

    Directory of Open Access Journals (Sweden)

    Wenrui Hao

    Full Text Available Atherosclerosis, the leading death in the United State, is a disease in which a plaque builds up inside the arteries. As the plaque continues to grow, the shear force of the blood flow through the decreasing cross section of the lumen increases. This force may eventually cause rupture of the plaque, resulting in the formation of thrombus, and possibly heart attack. It has long been recognized that the formation of a plaque relates to the cholesterol concentration in the blood. For example, individuals with LDL above 190 mg/dL and HDL below 40 mg/dL are at high risk, while individuals with LDL below 100 mg/dL and HDL above 50 mg/dL are at no risk. In this paper, we developed a mathematical model of the formation of a plaque, which includes the following key variables: LDL and HDL, free radicals and oxidized LDL, MMP and TIMP, cytockines: MCP-1, IFN-γ, IL-12 and PDGF, and cells: macrophages, foam cells, T cells and smooth muscle cells. The model is given by a system of partial differential equations with in evolving plaque. Simulations of the model show how the combination of the concentrations of LDL and HDL in the blood determine whether a plaque will grow or disappear. More precisely, we create a map, showing the risk of plaque development for any pair of values (LDL,HDL.

  7. The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model.

    Science.gov (United States)

    Hao, Wenrui; Friedman, Avner

    2014-01-01

    Atherosclerosis, the leading death in the United State, is a disease in which a plaque builds up inside the arteries. As the plaque continues to grow, the shear force of the blood flow through the decreasing cross section of the lumen increases. This force may eventually cause rupture of the plaque, resulting in the formation of thrombus, and possibly heart attack. It has long been recognized that the formation of a plaque relates to the cholesterol concentration in the blood. For example, individuals with LDL above 190 mg/dL and HDL below 40 mg/dL are at high risk, while individuals with LDL below 100 mg/dL and HDL above 50 mg/dL are at no risk. In this paper, we developed a mathematical model of the formation of a plaque, which includes the following key variables: LDL and HDL, free radicals and oxidized LDL, MMP and TIMP, cytockines: MCP-1, IFN-γ, IL-12 and PDGF, and cells: macrophages, foam cells, T cells and smooth muscle cells. The model is given by a system of partial differential equations with in evolving plaque. Simulations of the model show how the combination of the concentrations of LDL and HDL in the blood determine whether a plaque will grow or disappear. More precisely, we create a map, showing the risk of plaque development for any pair of values (LDL,HDL).

  8. ADSORPTION OF LDL ON THE MODIFIED CHITOSAN

    Institute of Scientific and Technical Information of China (English)

    LIUManying; ZHAOLirui; 等

    2000-01-01

    In this paper,the selective adsorption of LDL on chitosan modified with PEG and Asp.was studied.The adsorption rate of LDL and HDL on the double modified chitosan was 57% and 12% respoectively,The results shown that the double modified chitosan can be used a adsorbent for selective binding to LDL,this work may help to develop functional columns for hemoperfusion.

  9. Assimilation (in vitro) of cholesterol by yogurt bacteria.

    Science.gov (United States)

    Dilmi-Bouras, Abdelkader

    2006-01-01

    A considerable variation is noticed between the different species studied and even between the strains of the same species, in the assimilation of cholesterol in synthetic media, in presence of different concentrations of bile salts and under anaerobiosis conditions. The obtained results show that certain strains of Streptococcus thermophilus and Lactobacillus bulgaricus resist bile salts and assimilate appreciable cholesterol quantities in their presence. The study of associations shows that only strains assimilating cholesterol in a pure state remain active when they are put in associations, but there is no additional effect. However, the symbiotic effect between Streptococcus thermophilus and Lactobacillus bulgaricus of yogurt, with regard to bile salts, is confirmed. The lactic fermenters of yogurt (Y2) reduce the levels of total cholesterol, HDL-cholesterol and LDL-cholesterol, in a well-balanced way. In all cases, the assimilated quantity of HDL-cholesterol is lower than that of LDL-cholesterol. Moreover, yogurt Y2 keeps a significant number of bacteria, superior to 10(8) cells ml(-1), and has a good taste 10 days after its production.

  10. Lower low-density lipoprotein cholesterol levels are associated with Parkinson's disease.

    Science.gov (United States)

    Huang, Xuemei; Chen, Honglei; Miller, William C; Mailman, Richard B; Woodard, Jennifer L; Chen, Peter C; Xiang, Dong; Murrow, Richard W; Wang, Yi-Zhe; Poole, Charles

    2007-02-15

    The apolipoprotein E (APOE) epsilon2 allele has been associated with both Parkinson's disease (PD) and lower low-density lipoprotein cholesterol (LDL-C). We tested the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 112 controls. The PD cases were recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and the controls were recruited from the spouse populations of the same clinic. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated from unconditional logistic regressions, adjusting for age, gender, smoking status, and use of cholesterol-lowering agents. Lower LDL-C concentrations were associated with a higher occurrence of PD. Compared with participants with the highest LDL-C (> or =138 mg/dL), the OR was 2.2 (95% CI = 0.9-5.1) for participants with LDL-C of 115 to 137, 3.5 (95% CI = 1.6-8.1) for LDL-C of 93 to 114, and 2.6 (95% CI = 1.1-5.9) for LDL-C of < or = 92. Interestingly, use of either cholesterol-lowering drugs, or statins alone, was related to lower PD occurrence. Thus, our data provide preliminary evidence that low LDL-C may be associated with higher occurrence of PD, and/or that statin use may lower PD occurrence, either of which finding warrants further investigation.

  11. Implication of low HDL-c levels in patients with average LDL-c levels: a focus on oxidized LDL, large HDL subpopulation, and adiponectin.

    Science.gov (United States)

    Mascarenhas-Melo, Filipa; Sereno, José; Teixeira-Lemos, Edite; Marado, Daniela; Palavra, Filipe; Pinto, Rui; Rocha-Pereira, Petronila; Teixeira, Frederico; Reis, Flávio

    2013-01-01

    To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

  12. 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 perform...

  13. Elevated Cholesterol in the Coxiella burnetii Intracellular Niche Is Bacteriolytic

    Science.gov (United States)

    Mulye, Minal; Samanta, Dhritiman; Winfree, Seth; Heinzen, Robert A.

    2017-01-01

    ABSTRACT Coxiella burnetii is an intracellular bacterial pathogen and a significant cause of culture-negative endocarditis in the United States. Upon infection, the nascent Coxiella phagosome fuses with the host endocytic pathway to form a large lysosome-like vacuole called the parasitophorous vacuole (PV). The PV membrane is rich in sterols, and drugs perturbing host cell cholesterol homeostasis inhibit PV formation and bacterial growth. Using cholesterol supplementation of a cholesterol-free cell model system, we found smaller PVs and reduced Coxiella growth as cellular cholesterol concentration increased. Further, we observed in cells with cholesterol a significant number of nonfusogenic PVs that contained degraded bacteria, a phenotype not observed in cholesterol-free cells. Cholesterol had no effect on axenic Coxiella cultures, indicating that only intracellular bacteria are sensitive to cholesterol. Live-cell microscopy revealed that both plasma membrane-derived cholesterol and the exogenous cholesterol carrier protein low-density lipoprotein (LDL) traffic to the PV. To test the possibility that increasing PV cholesterol levels affects bacterial survival, infected cells were treated with U18666A, a drug that traps cholesterol in lysosomes and PVs. U18666A treatment led to PVs containing degraded bacteria and a significant loss in bacterial viability. The PV pH was significantly more acidic in cells with cholesterol or cells treated with U18666A, and the vacuolar ATPase inhibitor bafilomycin blocked cholesterol-induced PV acidification and bacterial death. Additionally, treatment of infected HeLa cells with several FDA-approved cholesterol-altering drugs led to a loss of bacterial viability, a phenotype also rescued by bafilomycin. Collectively, these data suggest that increasing PV cholesterol further acidifies the PV, leading to Coxiella death. PMID:28246364

  14. Endosomal cholesterol trafficking: protein factors at a glance

    Institute of Scientific and Technical Information of China (English)

    Ximing Du; Hongyuan Yang

    2013-01-01

    The delivery of low-density lipoprotein-derived cholesterol (LDL-C) from endosomal compartments to the plasma membrane and the endoplasmic reticulum (ER) is an important yet poorly understood cellular process.NiemannPick C1 (NPC1),a multi-pass integral membrane protein on the limiting membranes of late endosomes (LE)/lysosomes (Ly),is known to insert lumenal LDL-C to the limiting membrane of LE/Ly.Recent progress has identified novel cytoplasmic proteins that regulate the exit of LDL-C from LE/Ly,such as ORP5,a member of the oxysterolbinding protein-related protein (ORPs) family,and Hrs/VPS27,a well-established regulator of the endosomal sorting complex required for transport pathway.Whereas ORP5/ORPs may serve as cytosolic cholesterol carriers and deliver cholesterol in a non-vesicular manner,how Hrs/VPS27 regulate endosomal cholesterol sorting remains enigmatic.We discuss the functional relationship between NPC1,Hrs,and ORP5,and formulate possible schemes on how LDL-C may be moved from endosomal compartments to other cellular organelles.

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

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

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

  16. Cholesterol and triglycerides as biochemical markers of the state of the patient’s illness with acute lymphocytic leukemia

    OpenAIRE

    GUZMÁN, MARCO; Instituto de Enfermedades Neoplásicas; Sandoval, Miguel; Centro de Investigación de Bioquímica y Nutrición.

    2013-01-01

    Objective: To determine the relationship of cholesterol and triglycerides serum levels with the response to induction chemotherapy treatment in patients with acute lymphocytic leukemia. Material and Methods: The sample consisted in 25 patients 2 through 18 years-old admitted to the Neoplasia Diseases Institute with a recent diagnosis of acute lymphocytic leukemia in whom serum concentrations of total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides were determine, before and af...

  17. What Is Cholesterol?

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cholesterol KidsHealth > For Teens > Cholesterol Print A A A ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  18. What Is Cholesterol?

    Science.gov (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cholesterol KidsHealth > For Teens > Cholesterol A A A What's ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  19. EFFECT OF HERB-MEDICINE-CAKE-SEPARATED MOXIBUSTION ON SERUM LIPOPROTEIN CONTENTS AND RATIO OF HDL-Ch AND LDL-Ch IN HYPERLIPEMIA RABBITS

    Institute of Scientific and Technical Information of China (English)

    常小荣; 严洁; 岳增辉; 易受乡; 林亚平; 曹湘平; 沈菁

    2004-01-01

    Objective: To observe the effect of herb-medicine-cake-separated moxibustion on serum lipoprotein in hyperlipemia rabbits. Methods: 55 New-Zealand rabbits were randomly divided into control group (n=13), model group (n=14), direct moxibustion group (n=14) and herb-medicine-cake-separated moxibustion (indirect moxibustion) group (n=14). Hyperlipemia model was established by feeding the animals with specialized forage (15% vitellus powder, 5% lard, 0.5% cholesterol and common forage) for 6 weeks. Moxibustion was applied to "Juque"(CV 14), "Tianshu"(ST 25), "Fenglong"(ST 40), etc., 4 moxa-cones for every acupoint, once daily and continuously for 40 days. Serum high density lipoprotein-cholesterol (HDL-Ch), low density lipoprotein-cholesterol (LDL-Ch) and total cholesterol (TCh) contents were assayed with colorimetric method. Results: Compared with control group, serum LDL-Ch content, HDL-Ch/LDL-Ch and HDL-Ch/TCh of model group were significantly higher (P<0.05~0.01), while compared with model group, LDL-Ch contents of two moxibustion groups were strikingly lower (P<0.01). No significant differences were found between two moxibustion groups in all the 4 indexes. Conclusion: Both direct and indirect moxibustion can effectively lower serum LDL-Ch, raise HDL-Ch, HDL-Ch/LDL-Ch and HDL-Ch/TCh, and regulate lipoprotein metabolism in hyperlipemia rabbits.

  20. Chitosan oligosaccharides promote reverse cholesterol transport and expression of scavenger receptor BI and CYP7A1 in mice.

    Science.gov (United States)

    Zong, Chuanlong; Yu, Yang; Song, Guohua; Luo, Tian; Li, Luqin; Wang, Xinnong; Qin, Shucun

    2012-02-01

    Chitosan oligosaccharides (COS) are beneficial in improving plasma lipids and diminishing atherosclerotic risks. In this study, we examined the effects of COS on reverse cholesterol transport (RCT) in C57BL/6 mice. (3)H-cholesterol-laden macrophages were injected intraperitoneally into mice fed with various dosage of COS (250, 500, 1000 mg/kg mouse weight, respectively) or vehicle by gastric gavages. Plasma lipid level was determined and (3)H-cholesterol was traced in plasma, liver, bile and feces. The effects of COS on hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) and scavenger receptor BI (SR-BI) expression were also investigated. COS administration led to a significant decrease in plasma total cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in peritoneal macrophage-derived (3)H-cholesterol in liver and bile as well as in feces. Liver protein expressions of CYP7A1, SR-BI and LDL receptor (LDL-R) were improved in a dosage-dependent manner in COS-administered mice. Our findings provide the first in vivo demonstration of a positive role for COS in RCT pathway and hepatic CYP7A1 and SR-BI expression in mice. Additionally, the LDL cholesterol lowering effect might be relative to hepatic LDL-R expression stimulated by COS in mice.

  1. NEW CLASS OF DRUGS: THERAPEUTIC RNAi INHIBITION OF PCSK9 AS A SPECIFIC LDL-C LOWERING THERAPY.

    Science.gov (United States)

    Strat, A L; Ghiciuc, Cristina Mihaela; Lupuşoru, Cătălina Elena; Mitu, F

    2016-01-01

    Hyperlipidemia is a well-known risk factor for coronary heart disease, the leading cause of death for both men and women. Current lipid-lowering treatment is not always efficient, therefore new pharmacological interventions that reduce LDL cholesterol (LDL-C) have been developed. This paper presents new class of specific LDL lipid-lowering drugs under investigation in phase II or III clinical trials. The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a key enzyme in cholesterol homeostasis, improve the liver's ability to clear LDL from the plasma, reducing LDL-C levels. Currently, three monoclonal antibodies PCSK9 inhibitors (alirocumab, evolocumab and bococizumab) are evaluated in clinical outcome trials. ALN-PCSsc, the new first-in- class therapeutic RNA interference (RNAi) inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) is also the first-in-class investigational medicine that acts by turning off PCSK9 synthesis in the liver. The development leadership of ALN-PCSsc has now transferred from Alnylam Pharmaceuticals to The Medicines Company, who has initiated the ORION-1 Phase II study at the beginning of 2016. ALN-PCSsc has significant potential given its highly competitive profile as compared with monoclonal antibodies anti-PCSK9 MAbs, a recently approved class of LDL-C lowering drugs.

  2. LDL oxidation and extent of coronary atherosclerosis

    NARCIS (Netherlands)

    Vijver, L.P.L. van de; Kardinaal, A.F.M.; Duyvenvoorde, W. van; Kruijssen, D.A.C.M.; Grobbee, D.E.; Poppel, G. van; Princen, H.M.G.

    1998-01-01

    Accumulated evidence indicates that oxidative modification of LDL plays an important role in the atherogenic process. Therefore, we investigated the relation between coronary atherosclerosis and susceptibility of LDL to oxidation in a case-control study in men between 45 and 80 years of age. Case su

  3. Normal cholesterol levels with lovastatin (Mevinolin) therapy in a child with homozygous familial hypercholesterolemia following liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    East, C.; Grundy, S.M.; Bilheimer, D.W.

    1986-11-28

    Patients with homozygous familial hypercholesterolemia produce no normal low-density lipoprotein (LDL) receptors, and as a result, LDL accumulates in plasma, causing severe premature atherosclerosis. Two years ago, liver transplantation was performed in a child with homozygous familial hypercholesterolemia, restoring LDL receptor activity to about 60% of normal and reducing the LDL cholesterol level by 81%. However, the patient's lipoprotein levels remained significantly elevated for her age and sex. Treatment with lovastatin (mevinolin) one year after transplantation produced a marked improvement in the patient's lipoprotein profile. The total and LDL cholesterol levels fell 40% and 49%, respectively, to values within the normal range. The level of very low-density lipoprotein cholesterol fell 41%, and the level of total triglycerides declined 28%. While lovastatin therapy decreased the production rate of LDL by 35%, it did not affect the LDL fractional clearance rate. Thus, the combination of liver transplantation and lovastatin restored total and LDL cholesterol levels to normal in this patient with homozygous familial hypercholesterolemia.

  4. Attitudes and behavior of peripheral arterial disease patients toward influencing their physician's prescription of cholesterol-lowering medication.

    Science.gov (United States)

    McDermott, Mary M; Mazor, Kathleen M; Reed, George; Pagoto, Sherry; Graff, Rex; Merriam, Philip; Kibbe, Melina; Greenland, Philip; Ockene, Judy; Olendzki, Barbara; Huimin Tao; Ockene, Ira

    2010-04-01

    Among 355 peripheral arterial disease (PAD) patients with low density lipoprotein cholesterol (LDL-C) levels > or = 70 mg/dl, we assessed knowledge regarding optimal LDL levels and the importance of LDL-C-lowering therapy. We also assessed PAD participants' behaviors and attitudes regarding their engagement with their physician in treatment decisions for LDL-C lowering. The average baseline LDL-C level of participants was 103.4 mg/dl +/- 30.7 mg/dl. Seventy-six percent of participants were taking at least one cholesterol-lowering medication. Sixty-six percent were unable to define their optimal LDL-C. Only 47% strongly agreed that their own actions and decisions could reduce their LDL-C. Just 29.8% were aware that patients who request specific medications from their physician were more likely to receive them, and 16% had asked their physician whether they should be taking more cholesterol-lowering medication. These findings suggest that further study is needed to identify effective interventions to educate PAD patients and their physicians about the importance of cholesterol-lowering therapy and to encourage PAD patients to participate with their physician in decisions regarding cholesterol-lowering treatment. Clinical Trial Registration - URL: http://www.clinicaltrials.gov. Unique identifier: NCT00217919.

  5. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Blood Pressure Salt Million Hearts® WISEWOMAN Program High Cholesterol Facts Recommend on Facebook Tweet Share Compartir As ... the facts about high cholesterol [PDF-281K] . High Cholesterol in the United States 73.5 million adults ( ...

  6. Get Your Cholesterol Checked

    Science.gov (United States)

    ... Checked Print This Topic En español Get Your Cholesterol Checked Browse Sections The Basics Overview Cholesterol Test ... How often do I need to get my cholesterol checked? The general recommendation is to get your ...

  7. Dietary Fat and Cholesterol

    Science.gov (United States)

    ... Conditions Nutrition & Fitness Emotional Health Dietary Fat and Cholesterol Posted under Health Guides . Updated 7 March 2017. + ... saturated fat found in red meat. What is cholesterol? Cholesterol is a fatlike substance that’s found in ...

  8. Cholesterol lowering, low cholesterol, and mortality.

    Science.gov (United States)

    LaRosa, J C

    1993-10-01

    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  9. [The long-term therapy of familial hypercholesterolemia with heparin-induced extracorporeal LDL precipitation].

    Science.gov (United States)

    Roth, R; Köster, W; Wanner, C; Andre, M; Orth, M; Wieland, H; Schollmeyer, P

    1992-07-24

    The long-term tolerance to and effectiveness of heparin-induced extracorporeal LDL precipitation (HELP) in combination with lipid reducing drugs and diet was tested in six patient (5 males, 1 female; mean age 48 +/- 4 years). Follow-up period was over 50 months, in one patient over 24 months, while one man had a sudden cardiac death 57 weeks after starting treatment. The study was divided into three phases. In phase I (24 months) treatment consisted of HELP and conventional lipid-reducing drugs; in phase II (12 months) of lovastatin (80 mg daily) and cholestyramine (12-24 g daily); and phase III (14 months) of HELP, lovastatin and cholestyramine. In phase I it was possible to lower the pre-treatment level of LDL-cholesterol from 306 +/- 18 mg/dl to 173 +/- 13 mg/dl (43.5%). A similar effect (from 307 +/- 21 mg/dl to 155 +/- 17 mg/dl [-49.5%]) was obtained in phase II. The resumption of HELP reduced the pre-treatment LDL concentration to 136 +/- 9 mg/dl (-55.7%). The various treatment regimens were well tolerated. Biochemical data remained unchanged except for iron loss requiring substitution. Thus combined HELP, lovastatin and ion exchange offer for the first time an effective and reliable means in familial hypercholesterolaemia of clearly reducing long-term the mean LDL cholesterol level below the atherosclerosis threshold of 120 mg/dl.

  10. 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, Andre P.

    2010-01-01

    Objective: 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

  11. Effects of a very high saturated fat diet on LDL particles in adults with atherogenic dyslipidemia: A randomized controlled trial

    Science.gov (United States)

    Chiu, Sally; Williams, Paul T.

    2017-01-01

    Background Previous studies have shown that increases in LDL-cholesterol resulting from substitution of dietary saturated fat for carbohydrate or unsaturated fat are due primarily to increases in large cholesterol-enriched LDL, with minimal changes in small, dense LDL particles and apolipoprotein B. However, individuals can differ by their LDL particle distribution, and it is possible that this may influence LDL subclass response. Objective The objective of this study was to test whether the reported effects of saturated fat apply to individuals with atherogenic dyslipidemia as characterized by a preponderance of small LDL particles (LDL phenotype B). Methods Fifty-three phenotype B men and postmenopausal women consumed a baseline diet (55%E carbohydrate, 15%E protein, 30%E fat, 8%E saturated fat) for 3 weeks, after which they were randomized to either a moderate carbohydrate, very high saturated fat diet (HSF; 39%E carbohydrate, 25%E protein, 36%E fat, 18%E saturated fat) or low saturated fat diet (LSF; 37%E carbohydrate, 25%E protein, 37%E fat, 9%E saturated fat) for 3 weeks. Results Compared to the LSF diet, consumption of the HSF diet resulted in significantly greater increases from baseline (% change; 95% CI) in plasma concentrations of apolipoprotein B (HSF vs. LSF: 9.5; 3.6 to 15.7 vs. -6.8; -11.7 to -1.76; p = 0.0003) and medium (8.8; -1.3 to 20.0 vs. -7.3; -15.7 to 2.0; p = 0.03), small (6.1; -10.3 to 25.6 vs. -20.8; -32.8 to -6.7; p = 0.02), and total LDL (3.6; -3.2 to 11.0 vs. -7.9; -13.9 to -1.5; p = 0.03) particles, with no differences in change of large and very small LDL concentrations. As expected, total-cholesterol (11.0; 6.5 to 15.7 vs. -5.7; -9.4 to -1.8; psaturated fat intake. Conclusions Because medium and small LDL particles are more highly associated with cardiovascular disease than are larger LDL, the present results suggest that very high saturated fat intake may increase cardiovascular disease risk in phenotype B individuals. This trial

  12. Phytosterol ester constituents affect micellar cholesterol solubility in model bile.

    Science.gov (United States)

    Brown, Andrew W; Hang, Jiliang; Dussault, Patrick H; Carr, Timothy P

    2010-09-01

    Plant sterols and stanols (phytosterols) and their esters are nutraceuticals that lower LDL cholesterol, but the mechanisms of action are not fully understood. We hypothesized that intact esters and simulated hydrolysis products of esters (phytosterols and fatty acids in equal ratios) would differentially affect the solubility of cholesterol in model bile mixed micelles in vitro. Sodium salts of glycine- and taurine-conjugated bile acids were sonicated with phosphatidylcholine and either sterol esters or combinations of sterols and fatty acids to determine the amount of cholesterol solubilized into micelles. Intact sterol esters did not solubilize into micelles, nor did they alter cholesterol solubility. However, free sterols and fatty acids altered cholesterol solubility independently (no interaction effect). Equal contents of cholesterol and either campesterol, stigmasterol, sitosterol, or stigmastanol (sitostanol) decreased cholesterol solubility in micelles by approximately 50% compared to no phytosterol present, with stigmasterol performing slightly better than sitosterol. Phytosterols competed with cholesterol in a dose-dependent manner, demonstrating a 1:1 M substitution of phytosterol for cholesterol in micelle preparations. Unsaturated fatty acids increased the micelle solubility of sterols as compared with saturated or no fatty acids. No differences were detected in the size of the model micelles. Together, these data indicate that stigmasterol combined with saturated fatty acids may be more effective at lowering cholesterol micelle solubility in vivo.

  13. Reliability of Calculated Low-Density Lipoprotein Cholesterol.

    Science.gov (United States)

    Meeusen, Jeffrey W; Snozek, Christine L; Baumann, Nikola A; Jaffe, Allan S; Saenger, Amy K

    2015-08-15

    Aggressive low-density lipoprotein cholesterol (LDL-C)-lowering strategies are recommended for prevention of cardiovascular events in high-risk populations. Guidelines recommend a 30% to 50% reduction in at-risk patients even when LDL-C concentrations are between 70 and 130 mg/dl (1.8 to 3.4 mmol/L). However, calculation of LDL-C by the Friedewald equation is the primary laboratory method for routine LDL-C measurement. We compared the accuracy and reproducibility of calculated LDL-C <130 mg/dl (3.4 mmol/L) to LDL-C measured by β quantification (considered the gold standard method) in 15,917 patients with fasting triglyceride concentrations <400 mg/dl (4.5 mmol/L). Both variation and bias of calculated LDL-C increased at lower values of measured LDL-C. The 95% confidence intervals for a calculated LDL-C of 70 mg/dl (1.8 mmol/L) and 30 mg/dl (0.8 mmol/L) were 60 to 86 mg/dl (1.6 to 2.2 mmol/L) and 24 to 60 mg/dl (0.6 to 1.6 mmol/L), respectively. Previous recommendations have emphasized the requirement for a fasting sample with triglycerides <400 mg/dl (4.5 mmol/L) to calculate LDL-C by the Friedewald equation. However, no recommendations have addressed the appropriate lower reportable limit for calculated LDL-C. In conclusion, calculated LDL-C <30 mg/dl (0.8 mmol/L) should not be reported because of significant deviation from the gold standard measured LDL-C results, and caution is advised when using calculated LDL-CF values <70 mg/dl (1.8 mmol/L) to make treatment decisions.

  14. Genetic therapies to lower cholesterol.

    Science.gov (United States)

    Khoo, Bernard

    2015-01-01

    This review surveys the state-of-the-art in genetic therapies for familial hypercholesterolaemia (FH), caused most commonly by mutations in the LDL receptor (LDLR) gene. FH manifests as highly elevated low density lipoprotein (LDL) cholesterol levels and consequently accelerated atherosclerosis. Modern pharmacological therapies for FH are insufficiently efficacious to prevent premature cardiovascular disease, can cause significant adverse effects and can be expensive. Genetic therapies for FH have been mooted since the mid 1990s but gene replacement strategies using viral vectors have so far been unsuccessful. Other strategies involve knocking down the expression of Apolipoprotein B100 (APOB100) and the protease PCSK9 which designates LDLR for degradation. The antisense oligonucleotide mipomersen, which knocks down APOB100, is currently marketed (with restrictions) in the USA, but is not approved in Europe due to its adverse effects. To address this problem, we have devised a novel therapeutic concept, APO-skip, which is based on modulation of APOB splicing, and which has the potential to deliver a cost-effective, efficacious and safe therapy for FH.

  15. Increased Remnant Cholesterol Explains Part of Residual Risk of All-Cause Mortality in 5414 Patients with Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Jepsen, Anne-Marie K; Langsted, Anne; Varbo, Anette;

    2016-01-01

    Danish patients diagnosed with ischemic heart disease. Patients on statins were not excluded. Calculated remnant cholesterol was nonfasting total cholesterol minus LDL and HDL cholesterol. During 35836 person-years of follow-up, 1319 patients died. RESULTS: We examined both calculated and directly......BACKGROUND: Increased concentrations of remnant cholesterol are causally associated with increased risk of ischemic heart disease. We tested the hypothesis that increased remnant cholesterol is a risk factor for all-cause mortality in patients with ischemic heart disease. METHODS: We included 5414......: Increased concentrations of both calculated and measured remnant cholesterol were associated with increased all-cause mortality in patients with ischemic heart disease, which was not the case for increased concentrations of measured LDL cholesterol. This suggests that increased concentrations of remnant...

  16. Three-dimensional cryoEM reconstruction of native LDL particles to 16A resolution at physiological body temperature.

    Directory of Open Access Journals (Sweden)

    Vibhor Kumar

    Full Text Available BACKGROUND: Low-density lipoprotein (LDL particles, the major carriers of cholesterol in the human circulation, have a key role in cholesterol physiology and in the development of atherosclerosis. The most prominent structural components in LDL are the core-forming cholesteryl esters (CE and the particle-encircling single copy of a huge, non-exchangeable protein, the apolipoprotein B-100 (apoB-100. The shape of native LDL particles and the conformation of native apoB-100 on the particles remain incompletely characterized at the physiological human body temperature (37 °C. METHODOLOGY/PRINCIPAL FINDINGS: To study native LDL particles, we applied cryo-electron microscopy to calculate 3D reconstructions of LDL particles in their hydrated state. Images of the particles vitrified at 6 °C and 37 °C resulted in reconstructions at ~16 Å resolution at both temperatures. 3D variance map analysis revealed rigid and flexible domains of lipids and apoB-100 at both temperatures. The reconstructions showed less variability at 6 °C than at 37 °C, which reflected increased order of the core CE molecules, rather than decreased mobility of the apoB-100. Compact molecular packing of the core and order in a lipid-binding domain of apoB-100 were observed at 6 °C, but not at 37 °C. At 37 °C we were able to highlight features in the LDL particles that are not clearly separable in 3D maps at 6 °C. Segmentation of apoB-100 density, fitting of lipovitellin X-ray structure, and antibody mapping, jointly revealed the approximate locations of the individual domains of apoB-100 on the surface of native LDL particles. CONCLUSIONS/SIGNIFICANCE: Our study provides molecular background for further understanding of the link between structure and function of native LDL particles at physiological body temperature.

  17. Enhanced removal from the plasma of LDL-like nanoemulsion cholesteryl ester in trained men compared with sedentary healthy men.

    Science.gov (United States)

    Vinagre, Carmen G C; Ficker, Elisabeth S; Finazzo, Claudia; Alves, Maria J N; de Angelis, Katia; Irigoyen, Maria Claudia; Negrão, Carlos E; Maranhão, Raul C

    2007-10-01

    The objective of this study was to evaluate the effects of exercise training on plasma removal of a cholesterol-rich nanoemulsion (LDE) that mimics low-density lipoprotein (LDL) lipid structure and binds to LDL receptors. LDE-derived cholesteryl ester plasma kinetics was studied in 24 exercise-trained and 20 sedentary male subjects. LDE labeled with [(14)C]cholesteryl ester was injected intravenously, and plasma samples were collected over a 24-h period to determine radioisotope decay curves. LDL cholesterol concentration was similar in both groups. Fractional clearance rate (FCR) of the nanoemulsion label was greater in the exercise-trained group compared with the sedentary group (0.138 +/- 0.152 and 0.0261 +/- 0.023 h(-1), respectively). A positive correlation was found (r = 0.60, P < 0.01) between FCR and peak O(2) consumption in trained subjects. Circulating oxidized LDL levels were lower in trained subjects compared with the sedentary group (9.0 +/- 2.0 and 16.0 +/- 3.0 mU/l). LDE was also injected into control and LDL receptor gene knockout mice submitted and not submitted to training. Muscle LDE uptake percentage was increased in the trained mice compared with the untrained mice (1.1 +/- 0.8 and 0.2 +/- 0.1, respectively, P < 0.0001) in the control group but not in the knockout animals, indicating that the LDL receptor is involved in the increased uptake elicited by exercise. These results show that exercise training increases LDE plasma removal, which in turn suggests that it also increases LDL receptors or LDL receptor activity.

  18. Coincubation of PON1, APO A1, and LCAT increases the time HDL is able to prevent LDL oxidation.

    Science.gov (United States)

    Hine, David; Mackness, Bharti; Mackness, Mike

    2012-02-01

    The inhibition of low-density lipoprotein (LDL) oxidation by high-density lipoprotein (HDL) is a major antiatherogenic property of this lipoprotein. This activity is due, in part, to HDL associated proteins. However, whether these proteins interact in the antioxidant activity of HDL is unknown. LDL was incubated with apolipoprotein A1 (apo A1), lecithin:cholesterol acyltransferase (LCAT), and paraoxonase-1 (PON1) alone or in combination, in the presence or absence of HDL under oxidizing conditions. LDL lipid peroxide concentrations were determined. Apo A1, LCAT, and PON1 all inhibit LDL oxidation in the absence of HDL and enhance the ability of HDL to inhibit LDL oxidation. Their effect was additive rather than synergistic; the combination of these proteins significantly enhanced the length of time LDL was protected from oxidation. This seemed to be due to the ability of PON1 to prevent the oxidative inactivation of LCAT. Apo A1, LCAT, and PON1 can all contribute to the antioxidant activity of HDL in vitro. The combination of apo A1, LCAT, and PON1 prolongs the time that HDL can prevent LDL oxidation, due, at least in part, to the prevention LCAT inactivation.

  19. Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding.

    Science.gov (United States)

    Kallio, M J; Salmenperä, L; Siimes, M A; Perheentupa, J; Gylling, H; Miettinen, T A

    1997-04-01

    Our objective was to establish the role of the apoprotein (apo) E phenotype in determining serum cholesterol levels in infants fed exclusively on high-fat, high-cholesterol human milk and in those fed a low-cholesterol, high-unsaturated fat formula. The total and lipoprotein cholesterol, apoB, and triglyceride concentrations in serum were quantified and related to the apoE phenotype in 151 infants at birth and at 2, 6, 9, and 12 months of age. Forty-four had the E3/4 or 4/4 phenotype (E4 group), 94 had the E3/3 phenotype (E3 group), and 13 had the E2/3 or 2/4 phenotype (E2 group). In cord blood, cholesterol concentrations tended to be higher in the E4 than in the E2 group. With exclusive breast-feeding, the concentrations rose significantly faster and higher in the E4 group than in the E3 group or, especially, the E2 group. The values (mmol/L, mean +/- SEM) were 1.6 +/- 0.15, 1.5 +/- 0.05, 1.4 +/- 0.1 (P = n.s.) at birth; 4.2 +/- 0.1, 3.8 +/- 0.08, 3.4 +/- 0.2 (P HDL, HDL2, and HDL3 cholesterol concentrations did not depend on the apoE phenotype. Among infants fed high-fat, high-cholesterol human milk, the total and LDL-cholesterol concentrations and the LDL apoB concentration of those with the apoE phenotype 4/4 or 3/4 rose faster and to higher levels than in other infants. Among formula-fed infants, receiving a low-cholesterol, high-unsaturated fat diet, the differences between the apoE groups were smaller.

  20. Anti-atherosclerotic potential of gossypetin via inhibiting LDL oxidation and foam cell formation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jing-Hsien [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Chi-Ping [Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Hui-Hsuan, E-mail: linhh@csmu.edu.tw [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China)

    2013-10-15

    Gossypetin, a flavone originally isolated from Hibiscus species, has been shown to possess antioxidant, antimicrobial, and antimutagenic activities. Here, we investigated the mechanism(s) underlying the anti-atherosclerotic potential of gossypetin. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) scavenging activity assay showed that the addition of > 50 μM of gossypetin could scavenge over 50% of DPPH radicals. The inhibitory effects of gossypetin on the lipid and protein oxidation of LDL were defined by thiobarbituric acid reactive substance (TBARS) assay, the relative electrophoretic mobility (REM) of oxidized LDL (ox-LDL), and fragmentation of apoB in the Cu{sup 2+}-induced oxidation of LDL. Gossypetin showed potential in reducing ox-LDL-induced foam cell formation and intracellular lipid accumulation, and uptake ability of macrophages under non-cytotoxic concentrations. Molecular data showed that these influences of gossypetin might be mediated via peroxisome proliferator-activated receptor α (PPARα)/liver-X receptor α (LXRα)/ATP-binding cassette transporter A1 (ABCA1) and PPARγ/scavenger receptor CD36 pathways, as demonstrated by the transfection of PPARα siRNA or PPARγ expression vector. Our data implied that gossypetin regulated the PPAR signals, which in turn led to stimulation of cholesterol removal from macrophages and delay atherosclerosis. These results suggested that gossypetin potentially could be developed as an anti-atherosclerotic agent. - Highlights: • The anti-atherosclerotic effect of gossypetin in vitro was examined. • Gossypetin inhibited LDL oxidation. • Gossypetin showed potential in reducing on the formation of foam cells. • Gossypetin functions against ox-LDL through PPARa activation and PPARγ depression.

  1. Cooking for Lower Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Cooking for Lower Cholesterol Updated:Oct 28,2016 A heart-healthy eating ... content was last reviewed on 04/21/2014. Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  2. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmacogenetic analyses

    Directory of Open Access Journals (Sweden)

    Stott David J

    2011-10-01

    Full Text Available Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5. The top SNP (rs445925, chromosome 19 with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19 with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

  3. OxLDL up-regulates Niemann-Pick type C1 expression through ERK1/2/COX-2/ PPARα-signaling pathway in macrophages

    Institute of Scientific and Technical Information of China (English)

    Xiaohua yu; Chaoke Tang; Xiaoxu Li; Guojun Zhao; Ji Xiao; Zhongcheng Mo; Kai Yin; Zhisheng Jiang; Yuchang Fu; Xiaohui Zha

    2012-01-01

    The Niemann-Pick type C1 (NPC1) is located mainly in the membranes of the late endosome/lysosome and controls the intracellular cholesterol trafficking from the late endosome/lysosome to the plasma membrane.It has been reported that oxidized low-density lipoprotein (oxLDL) can up-regulate NPC1 expression.However,the detailed mechanisms are not fully understood.In this study,we investigated the effect of oxLDL stimulation on NPC1 expression in THP-1 macrophages.Our results showed that oxLDL up-regulated NPC1 expression at both mRNA and protein levels in a dose-dependent and time-dependent manner.In addition,oxLDL also induced the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2).Treatment with oxLDL significantly increased cyclooxygenase-2 (COX-2)mRNA and protein expression in the macrophages,and these increases were suppressed by the ERK1/2 inhibitor PD98059 or ERK1/2 small interfering RNA (siRNA) treatment.OxLDL up-regulated the expression of peroxisome proliferator-activated receptor α (PPARα) at the mRNA and protein levels,which could be abolished by COX-2 siRNA or COX-2 inhibitor NS398 treatment in these macrophages.OxLDL dramatically elevated cellular cholesterol efflux,which was abrogated by inhibiting ERK1/2 and/or COX-2.In addition,oxLDL-induced NPC1 expression and cellular cholesterol effiux were reversed by PPARα siRNA or GW6471,an antagonist of PPARα.Taken together,these results provide the evidence that oxLDL can up-regulate the expression of the NPC1 through ERK1/2/COX-2/PPARα-signaling pathway in macrophages.

  4. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde

    2010-01-01

    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  5. The ABCG5/8 Cholesterol Transporter and Myocardial Infarction Versus Gallstone Disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVES: The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone...... disease in opposite directions. BACKGROUND: High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation. METHODS: A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI...... and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated. RESULTS: Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5...

  6. Serum Oxidized LDL Levels in Type 2 Diabetic Patients with Retinopathy in Mthatha Region of the Eastern Cape Province of South Africa

    Directory of Open Access Journals (Sweden)

    Farzana Ganjifrockwala

    2016-01-01

    Full Text Available Oxidized low-density lipoprotein (ox-LDL is a powerful natural prooxidant derived from native LDL by cell-mediated oxidation. Such oxidation occurs more easily in glycated LDL as observed in diabetes mellitus. We evaluated and compared selected biomarkers of oxidative stress and total antioxidant (TAO levels in type 2 diabetes mellitus (T2DM patients with and without retinopathy in the Mthatha region of the Eastern Cape Province, South Africa. The participants totaled to 140 and this number comprised 98 diabetic patients on treatment, stratified by diabetes (54 and diabetes with retinopathy (44. Forty-two nondiabetic healthy controls made up the 140. Fasting plasma glucose (FPG, glycosylated hemoglobin (HbA1c, lipid profile, serum ox-LDL, thiobarbituric acid reactive substances (TBARS, and TAO levels were measured. A statistically significant increase in FPG, HbA1c, TBARS, and ox-LDL and a significant decrease in TAO levels were seen in T2DM patients with retinopathy as compared to controls. A significant negative correlation was observed between TAO and ox-LDL levels in the diabetic group. In multiple linear regression analyses, duration of diabetes, triglyceride, TAO, and LDL cholesterol were found to be significantly associated with ox-LDL. In multiple logistic regression analyses, ox-LDL [OR 1.02 (1.01–1.03, P=0.005] was the only risk factor and was significantly associated with the presence of retinopathy.

  7. A bovine papillomavirus-1 based vector restores the function of the low-density lipoprotein receptor in the receptor-deficient CHO-ldlA7 cell line

    Directory of Open Access Journals (Sweden)

    Ustav Mart

    2002-04-01

    Full Text Available Abstract Background The rationale of using bovine papillomavirus-1 (BPV-1 derived vectors in gene therapy protocols lies in their episomal maintenance at intermediate to high copy number, and stable, high-level expression of the gene products. We constructed the BPV-1 based vector harbouring the human low-density lipoprotein receptor (LDLR gene cDNA and tested its ability to restore the function of the LDLR in the receptor-deficient cell line CHO-ldlA7. Results The introduced vector p3.7LDL produced functionally active LDL receptors in the receptor-deficient cell line CHO-ldlA7 during the 32-week period of observation as determined by the internalisation assay with the labelled LDL particles. Conclusion Bovine papillomavirus type-1 (BPV-1-derived vectors could be suitable for gene therapy due to their episomal maintenance at intermediate to high copy number and stable, high-level expression of the gene products. The constructed BPV-1 based vector p3.7LDL produced functionally active LDL receptors in the LDLR-deficient cell line CHO-ldlA7 during the 32-week period of observation. In vivo experiments should reveal, whether 1–5% transfection efficiency obtained in the current work is sufficient to bring about detectable and clinically significant lowering of the amount of circulating LDL cholesterol particles.

  8. Blood cholesterol levels of hypercholesterolemic rat (Rattus norvegicus after VCO treatment

    Directory of Open Access Journals (Sweden)

    OKID PARAMA ASTIRIN

    2009-07-01

    Full Text Available Harini M, Astirin OP. 2009. Blood cholesterol levels of hypercholesterolemic rat (Rattus norvegicus after VCO treatment. Nusantara Bioscience 1: 53-58. This study aims to determine treatment effect of VCO on blood cholesterol levels in hypercholesterolemic white rat (Rattus norvegicus L.. This study used 25 male rats of Wistar strain divided into five treatment groups, namely: control, simvastatin (1.3 mL/270 g BW, cholesterol (9:1 lard, VCO 1 (1 mL/270 g BW, and VCO 2 (1.3 mL/270 g BW. Treatment was given orally. Total cholesterol, LDL and HDL cholesterol levels were measured at day 1, day 14 and day 28. Cholesterol data (total cholesterol, LDL and HDL were analyzed by Ancova and followed by contrast test at significance level of 5%.. The results showed that treatment of VCO at different doses significantly affected the decrease in blood total cholesterol, blood LDL levels, increasing blood HDL in hipercholesterolemic white rat.

  9. Effects of rosuvastatin on electronegative LDL as characterized by capillary isotachophoresis: the ROSARY Study

    OpenAIRE

    Zhang, Bo; Matsunaga, Akira; Rainwater, David L.; Miura, Shin-ichiro; Noda, Keita; Nishikawa, Hiroaki; Uehara, Yoshinari; Shirai, Kazuyuki; Ogawa, Masahiro; Saku, Keijiro

    2009-01-01

    Electronegative LDL, a charge-modified LDL (cm-LDL) subfraction that is more negatively charged than normal LDL, has been shown to be inflammatory. We previously showed that pravastatin and simvastatin reduced the electronegative LDL subfraction, fast-migrating LDL (fLDL), as analyzed by capillary isotachophoresis (cITP). The present study examined the effects of rosuvastatin on the more electronegative LDL subfraction, very-fast-migrating LDL (vfLDL), and small, dense charge-modified LDL (sd...

  10. Pengaruh Lama Pemberian Diet Tinggi Kolesterol terhadap Kadar LDL dan TGF-Β Serum Tikus Putih (Rattus novergicus strain Wistar

    Directory of Open Access Journals (Sweden)

    Biomechy Oktomalioputri

    2016-01-01

    Full Text Available AbstrakDiet tinggi kolesterol ini akan meningkatkan kadar Low Density Lipoprotein (LDL sebagai penanda hiperlipidemia yang berdampak pada terjadinya aterosklerosis. Transforming Growth Factor β (TGF-β memiliki peranan dalam proses terjadinya aterosklerosis ini. Keterlibatannya dalam hiperlipidemia sebagai faktor risiko utama aterosklerosis belum banyak diketahui. Tujuan penelitian ini adalah menentukan pengaruh lama permberian diet tinggi kolesterol terhadap kadar LDL dan TGF-β pada tikus putih (Rattus novergicus strain Wistar. Penelitian ini menggunakan metode post test only control group design yang dilakukan terhadap tikus Rattus novergicus jantan umur 3-4 bulan, berat 200-250 gram. Sampel penelitian terdiri dari 24 ekor tikus yang dibagi menjadi 4 kelompok, yaitu kelompok kontrol, A, B dan C. Selain kelompok kontrol, kelompok tikus diberi diet tinggi kolesterol berupa lemak kambing 10%, telur puyuh 5%, selama 10 hari untuk kelompok A, 20 hari untuk kelompok B dan 30 hari untuk kelompok C. Pada akhir percobaan darah tikus diambil dan dilakukan pemeriksaan kadar LDL dan TGF-β serum. Hasil penelitian diolah secara bivariat. Analisis yang digunakan yaitu uji oneway Anova. Hasil penelitian diketahui terdapat pengaruh lama pemberian diet tinggi kolesterol terhadap peningkatan kadar LDL serum tikus dengan p=0,01 (p<0,05. Terdapat pengaruh lama pemberian diet tinggi kolesterol terhadap penurunan kadar TGF-β dimana p=0,04 (p>0,05. Penelitian ini menyimpulkan bahwa terdapat pengaruh lama pemberian diet tinggi kolesterol terhadap kadar LDL dan tikus putih Rattus novergicus strain Wistar.Kata kunci: diet tinggi kolesterol, LDL, TGF-β AbstractHigh-cholesterol diet will increase Low Density Lipoprotein (LDL levels which impact to atherosclerosis. Transforming Growth Factor β (TGF-β play a role in atherosclerosis process. But its involvement in hyperlipidemia as the main risk factor of atherosclerosis still unknown. The objective of this study was

  11. PCSK9 inhibition-mediated reduction in Lp(a) with evolocumab: an analysis of 10 clinical trials and the LDL receptor's role.

    Science.gov (United States)

    Raal, Frederick J; Giugliano, Robert P; Sabatine, Marc S; Koren, Michael J; Blom, Dirk; Seidah, Nabil G; Honarpour, Narimon; Lira, Armando; Xue, Allen; Chiruvolu, Padmaja; Jackson, Simon; Di, Mei; Peach, Matthew; Somaratne, Ransi; Wasserman, Scott M; Scott, Rob; Stein, Evan A

    2016-06-01

    Lipoprotein (a) [Lp(a)] is independently associated with CVD risk. Evolocumab, a monoclonal antibody (mAb) to proprotein convertase subtilisin/kexin type 9 (PCSK9), decreases Lp(a). The potential mechanisms were assessed. A pooled analysis of Lp(a) and LDL cholesterol (LDL-C) in 3,278 patients from 10 clinical trials (eight phase 2/3; two extensions) was conducted. Within each parent study, biweekly and monthly doses of evolocumab statistically significantly reduced Lp(a) at week 12 versus control (P evolocumab, particularly in the setting of low circulating LDL, Lp(a) is reduced.

  12. Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia.

    Science.gov (United States)

    Austin, Melissa A; Edwards, Karen L; Monks, Stephanie A; Koprowicz, Kent M; Brunzell, John D; Motulsky, Arno G; Mahaney, Michael C; Hixson, James E

    2003-11-01

    Small, dense LDLs and hypertriglyceridemia, two highly correlated and genetically influenced risk factors, are known to predict for risk of coronary heart disease. The objective of this study was to perform a whole-genome scan for linkage to LDL size and triglyceride (TG) levels in 26 kindreds with familial hypertriglyceridemia (FHTG). LDL size was estimated using gradient gel electrophoresis, and genotyping was performed for 355 autosomal markers with an average heterozygosity of 76% and an average spacing of 10.2 centimorgans (cMs). Using variance components linkage analysis, one possible linkage was found for LDL size [logarithm of odds (LOD) = 2.1] on chromosome 6, peak at 140 cM distal to marker F13A1 (closest marker D6S2436). With adjustment for TG and/or HDL cholesterol, the LOD scores were reduced, but remained in exactly the same location. For TG, LOD scores of 2.56 and 2.44 were observed at two locations on chromosome 15, with peaks at 29 and 61 cM distal to marker D15S822 (closest markers D15S643 and D15S211, respectively). These peaks were retained with adjustment for LDL size and/or HDL cholesterol. These findings, if confirmed, suggest that LDL particle size and plasma TG levels could be caused by two different genetic loci in FHTG.

  13. High-density lipoprotein inhibits ox-LDL-induced adipokine secretion by upregulating SR-BI expression and suppressing ER Stress pathway.

    Science.gov (United States)

    Song, Guohua; Wu, Xia; Zhang, Pu; Yu, Yang; Yang, Mingfeng; Jiao, Peng; Wang, Ni; Song, Haiming; Wu, You; Zhang, Xiangjian; Liu, Huaxia; Qin, Shucun

    2016-07-29

    Endoplasmic reticulum stress (ERS) in adipocytes can modulate adipokines secretion. The aim of this study was to explore the protective effect of high-density lipoprotein (HDL) on oxidized low-density lipoprotein (ox-LDL)-induced ERS-C/EBP homologous protein (CHOP) pathway-mediated adipokine secretion. Our results showed that serum adipokines, including visfatin, resistin and TNF-α, correlated inversely with serum HDL cholesterol level in patients with abdominal obesity. In vitro, like ERS inhibitor 4-phenylbutyric acid (PBA), HDL inhibited ox-LDL- or tunicamycin (TM, an ERS inducer)-induced increase in visfatin and resistin secretion. Moreover, HDL inhibited ox-LDL-induced free cholesterol (FC) accumulation in whole cell lysate and in the endoplasmic reticulum. Additionally, like PBA, HDL inhibited ox-LDL- or TM-induced activation of ERS response as assessed by the decreased phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α and reduced nuclear translocation of activating transcription factor 6 as well as the downregulation of Bip and CHOP. Furthermore, HDL increased scavenger receptor class B type I (SR-BI) expression and SR-BI siRNA treatment abolished the inhibitory effects of HDL on ox-LDL-induced FC accumulation and CHOP upregulation. These data indicate that HDL may suppress ox-LDL-induced FC accumulation in adipocytes through upregulation of SR-BI, subsequently preventing ox-LDL-induced ER stress-CHOP pathway-mediated adipocyte inflammation.

  14. Reasons for the upsetting cholesterol level during the community investigation from residents, physicians, and social aspects: The China Cholesterol Education Program (CCEP)

    Institute of Scientific and Technical Information of China (English)

    XIE Jiang; GUAN Fei; WANG Jia-hong; HU Da-yi

    2011-01-01

    Background The community medical center is the first barrier for lipid control. We aimed to survey the residents' cholesterol condition in the community, and pursue the reasons for the upsetting results from various aspects.Methods Residents and physicians were recruited from four community centers. Residents completed questionnaires and a physical examination as well as biochemical analysis. Physicians were also asked to complete a questionnaire,some of which were about basic knowledge of lipids.Results About 37.0% male and 48.1% female had elevated cholesterol levels. Residents' blood pressure (BP), fasting glucose (FG), body mass index (BMI), and waist circumference (WC) were positively associated with their low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). Framingham risk scoring (FRS) was strongly related to cholesterol (P <0.001 for LDL-C and TC). Residents' higher education grade was positively related to a normal cholesterol condition (P<0.001), while personal income was negatively related to it. Rural residents had higher percent of population with normal cholesterol level (normal cholesterol rate) than their city counterpart (P <0.001). Although physicians with college education had a much higher lipid knowledge level themselves, the physicians' factors had almost no relationship with the residents' cholesterol levels.Conclusions Management of hypercholesterolemia should be an important component of health strategy in Beijing.Education is imperative for residents as well as for physicians.

  15. Acute sterol o-acyltransferase 2 (SOAT2 knockdown rapidly mobilizes hepatic cholesterol for fecal excretion.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

    Full Text Available The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE. We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2 increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD, the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion.

  16. Oxidized LDL lipids increase β-amyloid production by SH-SY5Y cells through glutathione depletion and lipid raft formation.

    Science.gov (United States)

    Dias, Irundika H K; Mistry, Jayna; Fell, Shaun; Reis, Ana; Spickett, Corinne M; Polidori, Maria C; Lip, Gregory Y H; Griffiths, Helen R

    2014-10-01

    Elevated total cholesterol in midlife has been associated with increased risk of dementia in later life. We have previously shown that low-density lipoprotein (LDL) is more oxidized in the plasma of dementia patients, although total cholesterol levels are not different from those of age-matched controls. β-Amyloid (Aβ) peptide, which accumulates in Alzheimer disease (AD), arises from the initial cleavage of amyloid precursor protein by β-secretase-1 (BACE1). BACE1 activity is regulated by membrane lipids and raft formation. Given the evidence for altered lipid metabolism in AD, we have investigated a mechanism for enhanced Aβ production by SH-SY5Y neuronal-like cells exposed to oxidized LDL (oxLDL). The viability of SH-SY5Y cells exposed to 4μg oxLDL and 25µM 27-hydroxycholesterol (27OH-C) was decreased significantly. Lipids, but not proteins, extracted from oxLDL were more cytotoxic than oxLDL. In parallel, the ratio of reduced glutathione (GSH) to oxidized glutathione was decreased at sublethal concentrations of lipids extracted from native and oxLDL. GSH loss was associated with an increase in acid sphingomyelinase (ASMase) activity and lipid raft formation, which could be inhibited by the ASMase inhibitor desipramine. 27OH-C and total lipids from LDL and oxLDL independently increased Aβ production by SH-SY5Y cells, and Aβ accumulation could be inhibited by desipramine and by N-acetylcysteine. These data suggest a mechanism whereby oxLDL lipids and 27OH-C can drive Aβ production by GSH depletion, ASMase-driven membrane remodeling, and BACE1 activation in neuronal cells.

  17. Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

    Institute of Scientific and Technical Information of China (English)

    Katriina; Nemes; Fredrik; ?berg; Helena; Gylling; Helena; Isoniemi

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

  18. The pivotal role of cholesterol absorption inhibitors in the management of dyslipidemia

    Directory of Open Access Journals (Sweden)

    Suleiman Ehab S

    2004-10-01

    Full Text Available Abstract Elevated low-density lipoprotein (LDL-cholesterol is associated with a significantly increased risk of coronary heart disease. Ezetimibe is the first member of a new class of selective cholesterol absorption inhibitors. It impairs the intestinal reabsorption of both dietary and hepatically excreted biliary cholesterol. Ezetimibe is an effective and safe agent for lowering LDL-C and non HDL-C. Short term clinical trials have established the role of ezetimibe monotherapy and its use in combination with statins. Furthermore, ezetimibe and statin combination therapy increased the percentage of patients who achieved their LDL-C treatment goal. Studies using surrogate markers of atherosclerosis have suggested a possible role of ezetimibe in combating atherosclerosis. Ezetimibe provides an effective therapeutic strategy for the management of homozygous familial hypercholesterolemia (HoFH and sitosterolemia. The lack of outcomes and long term safety data is attributed to the relatively recent introduction of this medication.

  19. An enzyme thermistor-based assay for total and free cholesterol.

    Science.gov (United States)

    Raghavan, V; Ramanathan, K; Sundaram, P V; Danielsson, B

    1999-11-01

    A method to evaluate the free (FC) and total cholesterol (TC) in human serum, bile and gallstone extract using an enzyme thermistor (ET)-based flow injection analysis (FIA) is presented. The cholesterol in high-density (HDL-C) and low density lipoprotein (LDL-C) have also been evaluated. A heparin functionalized Sepharose column was employed for the isolation of HDL and LDL fractions from serum. The estimation of cholesterol and its esters was based on their reaction with cholesterol oxidase (CO), cholesterol esterase (CE) and catalase (CAT). Three different enzyme columns, i.e. co-immobilized CO/CAT (column A), only CE (column B) and co-immobilized CO/CE/CAT (column C) were prepared by cross-linking the enzymes on glass beads using glutaraldehyde. Column A was used for estimating FC and column C was used for estimating total cholesterol (cholesterol plus esterified cholesterol). Column B was used as a pre-column which could be switched 'in' or 'out' in conjunction with column A for the estimation of TC or FC, respectively. A calibration between 1.0 and 8.0 mmol/l for FC and 0. 25 and 4.0 mmol/l for TC was obtained. For more than 2000 assays with the ET device a C.V. of less than 4% was obtained. The assay time was approximately 4 min per assay. The cholesterol estimations on the ET correlated well with similar estimations using a commercially available cholesterol diagnostic kit.

  20. Cholesterol acceptor capacity is preserved by different mechanisms in preterm and term fetuses.

    Science.gov (United States)

    Pecks, Ulrich; Mohaupt, Markus G; Hütten, Matthias C; Maass, Nicolai; Rath, Werner; Escher, Geneviève

    2014-02-01

    Fetal serum cholesterol and lipoprotein concentrations differ between preterm and term born neonates. An imbalance of the flow of cholesterol from the sites of synthesis or efflux from cells of peripheral organs to the liver, the reverse cholesterol transport (RCT), is linked to atherosclerosis and cardiovascular disease (CVD). Preterm delivery is a risk factor for the development of CVD. Thus, we hypothesized that RCT is affected by a diminished cholesterol acceptor capacity in preterm as compared to term fetuses. Cholesterol efflux assays were performed in RAW264.7, HepG2, and HUVEC cell lines. In the presence and absence of ABC transporter overexpression by TO-901317, umbilical cord sera of preterm and term born neonates (n = 28 in both groups) were added. Lipid components including high density lipoprotein (HDL), low density lipoprotein (LDL), apolipoprotein A1, and apolipoprotein E were measured and related to fractional cholesterol efflux values. We found overall, fractional cholesterol efflux to remain constant between the study groups, and over gestational ages at delivery, respectively. However, correlation analysis revealed cholesterol efflux values to be predominantly related to HDL concentration at term, while in preterm neonates, cholesterol efflux was mainly associated with LDL In conclusion cholesterol acceptor capacity during fetal development is kept in a steady state with different mechanisms and lipid fractions involved at distinct stages during the second half of fetal development. However, RCT mechanisms in preterm neonates seem not to be involved in the development of CVD later in life suggesting rather changes in the lipoprotein pattern causative.

  1. Study of Lipid Profile in Obese Individuals and the Effect of Cholesterol Lowering Agents on Them

    Directory of Open Access Journals (Sweden)

    Surajit Kumar Mukhopadhyay

    2012-04-01

    Full Text Available Objectives: To study the effect of cholesterol lowering agents on lipid profile in obese patients. Background: Obesity leads to morbidity as well as mortality. There is usually increased level of total cholesterol, LDL- cholesterol, VLDL- cholesterol, triglycerides and decreased level of HDL- cholesterol in obesity. These are the risk factors for cardiovascular disease, hypertension, diabetes mellitus, pulmonary disorder and gall stones. Method: Thirty obese patients received treatment with Lovastatin along with dietary measures, compared with age and sex matched controls- before and after 6 weeks of therapy, presented in a table and results were analysed using student's "t" test (both paired and unpaired. Result: There was significant reduction in total cholesterol as well as LDL- cholesterol; HDL- cholesterol was also increased significantly. But triglycerides and VLDL- cholesterol showed small but significant increase. Conclusion: Cholesterol lowering agents like Lovastatin was quite effective when used long-term in dyslipidaemia in obesity towards reduction of risk factors for cardiovascular diseases, strokes, etc. Hypertriglyceridaemia should also be treated adequately

  2. 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

  3. Linkage of the cholesterol 7α-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study

    Institute of Scientific and Technical Information of China (English)

    Jing-Ping Lin; Richard H. Myers; Laura Almasy; Hilary H. Coon; Donna K. Arnett; Yuling Hong; Steven C. Hunt

    2005-01-01

    Background Genetic factors account for approximately 50% of the individual variation in plasma low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7α-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR), three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly.Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases.

  4. 豚鼠高脂血症模型LDL-C代谢紊乱的机制研究%Mechanism of hyperlipidemic LDL-C metabolic disorder in the guinea pig

    Institute of Scientific and Technical Information of China (English)

    宋鑫; 高南南; 杨润梅; 刘芳

    2012-01-01

    目的 建立豚鼠高胆固醇血症模型,并对形成机制进行探讨.方法 高脂饲料诱导法建立豚鼠高胆固醇血症模型,分别于造模1、2、4周检测血清脂质的动态变化;检测肝脏脂质;酶联免疫分析法测定血清ox-LDL浓度;实时荧光定量PCR法检测肝脏CYP7A1(cholesterol 7a-hydroxylase A1)、肝脏法尼酯X受体(hepatic farnesoid X receptor,FXR)、肝X受体α(liver X receptor,LXRα)、HMG-CoA还原酶mRNA的相对表达;Western blot法检测肝脏LDL-R的蛋白表达情况.结果 豚鼠经高脂饲料诱导1周后,模型组与对照组比较血清TC、LDL-C即发生升高,随造模时间延长,血脂一直维持在较高水平.造模4周后模型组血清ox-LDL、sd-LDL浓度,肝脏TC水平比正常组升高.肝脏HMG-CoA还原酶表达下调,LDL-R蛋白表达量明显高于正常组.值得注意的是豚鼠肝脏法尼酯X受体(FXR)表达明显上调,且肝X受体α(LXRα)表达也明显上调,但二者激活水平相当,最终未改变肝脏CYP7A1mRNA的表达水平.结论 高脂诱导豚鼠形成高胆固醇血症主要与外源性胆固醇和低密度脂蛋白的清除发生障碍有关.%Aim To establish the hyperlipidemic guinea pig model and investigate the mechanism of development. Methods Experimental hyperlipidemic guinea pig model induced by high-cholesterol diets was established. Serum lipids were determined after modeling 1, 2 and 4 weeks, and the concentration of ox-LDL was also determined by ELISA. Real-time polymerase chain reaction to measure the expressions of CYP7A1, FXR, LXRa and HMG-CoA reductase Mrna. LDL-R was measured by western blot. Results In comparison with control group, serum TC and LDL-C were significantly increased after fed with high cholesterol diet for 1 week, and as time went by, the serum lipids remained at a high level. The concentrations of serum ox-LDL and sd-LDL were also increased. The model group had a greater accumulation of total cholesterol inthe liver compared with

  5. The relationship between LDL oxidation and macrophage myeloperoxidase activity

    Institute of Scientific and Technical Information of China (English)

    武军驻; 刘艳红; 李小明; 陈丽达; 夏腊菊; 洪嘉玲

    2003-01-01

    Objective To explore low density lipoprotein (LDL) oxidation by macrophage myeloperoxidase (MPO) at molecular level.Methods Using a mouse macrophage model, we examined the relationship between LDL oxidation and macrophage MPO by measuring macrophage MPO activity, LDL oxidation products, MPO gene expression and cellular orientation of LDL oxidation. Results MPO gene expression increased to its maximum gradually when the concentration of LDL was increased, and then maintained at that level. NaN3 inhibied the elevation of MPO activity and LDL oxidation, which was LDL concentration-dependent. After the composition of macrophage membrane was roughly analyzed, it was determined that the contents of MPO and LDL in 5% sucrose were 7.667 and 21 times higher than those in 10% sucrose, respectively. Conclusion LDL is attached to the "microdomain" of the macrophage membrane in which LDL is oxidized by MPO.

  6. Pitavastatin Differentially Modulates MicroRNA-Associated Cholesterol Transport Proteins in Macrophages.

    Directory of Open Access Journals (Sweden)

    Haijun Zhang

    Full Text Available There is emerging evidence identifying microRNAs (miRNAs as mediators of statin-induced cholesterol efflux, notably through the ATP-binding cassette transporter A1 (ABCA1 in macrophages. The objective of this study was to assess the impact of an HMG-CoA reductase inhibitor, pitavastatin, on macrophage miRNAs in the presence and absence of oxidized-LDL, a hallmark of a pro-atherogenic milieu. Treatment of human THP-1 cells with pitavastatin prevented the oxLDL-mediated suppression of miR-33a, -33b and -758 mRNA in these cells, an effect which was not uniquely attributable to induction of SREBP2. Induction of ABCA1 mRNA and protein by oxLDL was inhibited (30% by pitavastatin, while oxLDL or pitavastatin alone significantly induced and repressed ABCA1 expression, respectively. These findings are consistent with previous reports in macrophages. miRNA profiling was also performed using a miRNA array. We identified specific miRNAs which were up-regulated (122 and down-regulated (107 in THP-1 cells treated with oxLDL plus pitavastatin versus oxLDL alone, indicating distinct regulatory networks in these cells. Moreover, several of the differentially expressed miRNAs identified are functionally associated with cholesterol trafficking (six miRNAs in cells treated with oxLDL versus oxLDL plus pitavastatin. Our findings indicate that pitavastatin can differentially modulate miRNA in the presence of oxLDL; and, our results provide evidence that the net effect on cholesterol homeostasis is mediated by a network of miRNAs.

  7. Weight loss associated with reduced intake of carbohydrate reduces the atherogenicity of LDL in premenopausal women.

    Science.gov (United States)

    Lofgren, Ingrid; Zern, Tosca; Herron, Kristin; West, Kristy; Sharman, Matthew J; Volek, Jeff S; Shachter, Neil S; Koo, Sung I; Fernandez, Maria Luz

    2005-09-01

    The effect of a 3-tier intervention including dietary modifications (ie, moderate energy restriction, decreased carbohydrate, increased protein), increased physical activity, and the use of carnitine as a dietary supplement was evaluated on plasma lipids and the atherogenicity of low-density lipoprotein (LDL) particles in a population of overweight and obese premenopausal (aged 20-45 years) women. Carnitine or a placebo (cellulose) was randomly assigned to the participants using a double-blind design. Carnitine supplementation was postulated to enhance fat oxidation resulting in lower concentrations of plasma triglycerides. Seventy women completed the 10-week protocol, which followed a reduction in their energy intake by 15% and a macronutrient energy distribution of 30% protein, 30% fat, and 40% carbohydrate. In addition, subjects increased the number of steps taken per day by 4500. As no differences were observed between the carnitine and placebo groups in all the measured parameters, all subjects were pooled together for statistical analysis. Participants decreased (Pweight, plasma total cholesterol, LDL cholesterol, and triglyceride were decreased by 4.5%, 8.0%, 12.3%, and 19.2% (Pweight loss (weight) associated with reduced caloric intake, lower dietary carbohydrate, and increased physical activity impacts the atherogenicity of LDL.

  8. Induction of DKK1 by ox-LDL negatively regulates intracellular lipid accumulation in macrophages.

    Science.gov (United States)

    Zhang, Yu; Ge, Cheng; Wang, Lin; Liu, Xinxin; Chen, Yifei; Li, Mengmeng; Zhang, Mei

    2015-01-01

    Dickkopf1 (DKK1), a canonical Wnt/β-catenin pathway antagonist, is closely associated with cardiovascular disease and adipogenesis. We performed an in vitro study to determine whether oxidized low-density lipoprotein (ox-LDL) increased the expression of DKK1 in macrophages and whether β-catenin and liver X receptor α (LXRα) were involved in this regulation. Induction of DKK1 expression by ox-LDL decreased the level of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) via a Wnt/β-catenin pathway and increased ATP-binding cassette transporter A/G1 (ABCA/G1) levels via a signal transducer and activator of transcription 3 (STAT3) pathway. Lower LOX-1 and higher ABCA/G1 levels inhibited cholesterol loading in macrophages. In conclusion, ox-LDL may induce DKK1 expression in macrophages to inhibit the accumulation of lipids through a mechanism that involves downregulation of LOX-1-mediated lipid uptake and upregulation of ABCA/G1-dependent cholesterol efflux.

  9. 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), trigylcerides, or lipid ratios, and how they compare with on-treatment LDL-C....

  10. Stanol esters attenuate the aggravating effect of dietary cholesterol on atherosclerosis in homozygous Watanabe rabbits

    DEFF Research Database (Denmark)

    Schrøder, Malene; Husche, Constanze; Pilegaard, Kirsten

    2009-01-01

    Plant stanols are marketed as natural means to lower blood cholesterol in humans; hence the effect on combined familial hyperlipidemia is not known. The objective was to investigate the effect of stanol esters on blood lipids and aortic atherosclerosis in homozygous WHHL rabbits challenged...... with dietary cholesterol. A total of 36 rabbits, 6 weeks of age, with initial plasma cholesterol of 22.5 mmol/L were assigned to two treatment groups fed a standard rabbit chow with 1 g/kg cholesterol or this diet added 34 g/kg stanol ester, respectively, for 16 weeks. Plasma cholesterol was measured initially...... and at termination, also in lipoproteins. Aortic atherosclerosis was evaluated as cholesterol content and area covered by plaque. Plasma cholesterol was not significantly different between the groups at termination (35.7 mmol/L vs. 35.5 mmol/L). A significant increase in LDL was seen (13.1 mmol/L vs. 16.5 mmol...

  11. Trypanosoma cruzi Epimastigotes Are Able to Manage Internal Cholesterol Levels under Nutritional Lipid Stress Conditions

    Science.gov (United States)

    Pereira, Miria Gomes; Visbal, Gonzalo; Salgado, Leonardo T.; Vidal, Juliana Cunha; Godinho, Joseane L. P.; De Cicco, Nuccia N. T.; Atella, Geórgia C.; de Souza, Wanderley; Cunha-e-Silva, Narcisa

    2015-01-01

    Trypanosoma cruzi epimastigotes store high amounts of cholesterol and cholesteryl esters in reservosomes. These unique organelles are responsible for cellular digestion by providing substrates for homeostasis and parasite differentiation. Here we demonstrate that under nutritional lipid stress, epimastigotes preferentially mobilized reservosome lipid stocks, instead of lipid bodies, leading to the consumption of parasite cholesterol reservoirs and production of ergosterol. Starved epimastigotes acquired more LDL-NBD-cholesterol by endocytosis and distributed the exogenous cholesterol to their membranes faster than control parasites. Moreover, the parasites were able to manage internal cholesterol levels, alternating between consumption and accumulation. With normal lipid availability, parasites esterified cholesterol exhibiting an ACAT-like activity that was sensitive to Avasimibe in a dose-dependent manner. This result also implies that exogenous cholesterol has a role in lipid reservoirs in epimastigotes. PMID:26068009

  12. The cholesterol lowering property of coriander seeds (Coriandrum sativum): mechanism of action.

    Science.gov (United States)

    Dhanapakiam, P; Joseph, J Mini; Ramaswamy, V K; Moorthi, M; Kumar, A Senthil

    2008-01-01

    Coriandrum sativum (Coriander) has been documented as a traditional treatment for cholesterol and diabetes patients. In the present study, coriander seeds incorporated into diet and the effect of the administration of coriander seeds on the metabolism of lipids was studied in rats, fed with high fat diet and added cholesterol. The seeds had a significant hypolipidemic action. In the experimental group of rats (tissue) the level of total cholesterol and triglycerides increased significantly There was significant increase in beta-hydroxy, beta-methyl glutaryl CoA reductase and plasma lecithin cholesterol acyl transferase activity were noted in the experimental group. The level of low density lipoprotein (LDL) + very low density lipoprotein (VLDL) cholesterol decreased while that of high density lipoprotein (HDL) cholesterol increased in the experimental group compared to the control group. The increased activity of plasma LCAT enhanced degradation of cholesterol to fecal bile acids and neutral sterols appeared to account for its hypocholesterolemic effect.

  13. Safety profile of subjects treated to very low low-density lipoprotein cholesterol levels (JUPITER).

    Science.gov (United States)

    Everett, Brendan M; Mora, Samia; Glynn, Robert J; MacFadyen, Jean; Ridker, Paul M

    2014-12-01

    Recent US guidelines expand the indications for high-intensity statin therapy, yet data on the safety of attaining very low-density lipoprotein cholesterol (LDL-C) levels are scarce. Among 16,304 participants in the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) with on-treatment LDL-C levels, we identified 767 who did and 7,387 who did not achieve LDL-C JUPITER, achieving LDL-C levels <30 mg/dl with high-intensity statin therapy appeared to be generally well tolerated but associated with certain adverse events, including more physician-reported diabetes, hematuria, hepatobiliary disorders, and insomnia. These data may guide the monitoring of patients on intensive statin therapy and adverse events in trials of therapies that lead to very low LDL-C levels.

  14. Controlling Cholesterol with Statins

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

  15. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  16. Cholesterol and public policy.

    Science.gov (United States)

    LaRosa, J C

    1994-08-01

    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  17. High blood cholesterol levels

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000403.htm High blood cholesterol levels To use the sharing features ... stroke, and other problems. The medical term for high blood cholesterol is lipid disorder, hyperlipidemia, or hypercholesterolemia. ...

  18. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

    Science.gov (United States)

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi

    2015-11-27

    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

  19. Cholesterol-lowering properties of Ganoderma lucidum in vitro, ex vivo, and in hamsters and minipigs

    Directory of Open Access Journals (Sweden)

    Hajjaj H

    2004-02-01

    Full Text Available Abstract Introduction There has been renewed interest in mushroom medicinal properties. We studied cholesterol lowering properties of Ganoderma lucidum (Gl, a renowned medicinal species. Results Organic fractions containing oxygenated lanosterol derivatives inhibited cholesterol synthesis in T9A4 hepatocytes. In hamsters, 5% Gl did not effect LDL; but decreased total cholesterol (TC 9.8%, and HDL 11.2%. Gl (2.5 and 5% had effects on several fecal neutral sterols and bile acids. Both Gl doses reduced hepatic microsomal ex-vivo HMG-CoA reductase activity. In minipigs, 2.5 Gl decreased TC, LDL- and HDL cholesterol 20, 27, and 18%, respectively (P Conclusions Overall, Gl has potential to reduce LDL cholesterol in vivo through various mechanisms. Next steps are to: fully characterize bioactive components in lipid soluble/insoluble fractions; evaluate bioactivity of isolated fractions; and examine human cholesterol lowering properties. Innovative new cholesterol-lowering foods and medicines containing Gl are envisioned.

  20. Alginic acid cell entrapment: a novel method for measuring in vivo macrophage cholesterol homeostasis

    Science.gov (United States)

    Sontag, Timothy J.; Chellan, Bijoy; Bhanvadia, Clarissa V.; Getz, Godfrey S.; Reardon, Catherine A.

    2015-01-01

    Macrophage conversion to atherosclerotic foam cells is partly due to the balance of uptake and efflux of cholesterol. Cholesterol efflux from cells by HDL and its apoproteins for subsequent hepatic elimination is known as reverse cholesterol transport. Numerous methods have been developed to measure in vivo macrophage cholesterol efflux. Most methods do not allow for macrophage recovery for analysis of changes in cellular cholesterol status. We describe a novel method for measuring cellular cholesterol balance using the in vivo entrapment of macrophages in alginate, which retains incorporated cells while being permeable to lipoproteins. Recipient mice were injected subcutaneously with CaCl2 forming a bubble into which a macrophage/alginate suspension was injected, entrapping the macrophages. Cells were recovered after 24 h. Cellular free and esterified cholesterol mass were determined enzymatically and normalized to cellular protein. Both normal and cholesterol loaded macrophages undergo measureable changes in cell cholesterol when injected into WT and apoA-I-, LDL-receptor-, or apoE-deficient mice. Cellular cholesterol balance is dependent on initial cellular cholesterol status, macrophage cholesterol transporter expression, and apolipoprotein deficiency. Alginate entrapment allows for the in vivo measurement of macrophage cholesterol homeostasis and is a novel platform for investigating the role of genetics and therapeutic interventions in atherogenesis. PMID:25465389

  1. The food matrix and sterol characteristics affect the plasma cholesterol lowering of phytosterol/phytostanol.

    Science.gov (United States)

    Cusack, Laura Kells; Fernandez, Maria Luz; Volek, Jeff S

    2013-11-01

    Foods with added phytosterols/phytostanols (PS) are recommended to lower LDL cholesterol (LDL-c) concentrations. Manufacturers have incorporated PS into a variety of common foods. Understanding the cholesterol-lowering impact of the food matrix and the PS characteristics would maximize their success and increase the benefit to consumers. This review systematically examines whether the PS characteristics and the fatty acid composition of foods with added PS affects serum LDL-c. A total of 33 studies published between the years 1998 and 2011 inclusive of 66 individual primary variables (strata) were evaluated. The functional food matrices included margarine, mayonnaise, yogurt, milk, cheese, meat, grain, juice, and chocolate. Consistently, ≥10% reductions in LDL-c were reported when the characteristics of the food matrix included poly- and monounsaturated fatty acids known to lower LDL-c. Also, >10% mean reductions in LDL-c were reported when β-sitostanol and campestanol as well as stanol esters were used. These characteristics allow both low-fat and high-fat foods to successfully incorporate PS and significantly lower LDL-c.

  2. The macrophage Ox-LDL receptor, CD36 and its association with type II diabetes mellitus.

    Science.gov (United States)

    Gautam, Sunaina; Banerjee, Monisha

    2011-04-01

    Type II diabetes mellitus (T2DM) is a common and serious metabolic disorder worldwide. It is the third leading cause of death after cancer and cardiovascular disease (CVD). Over time, diabetes mellitus can lead to different complications like atherosclerosis, coronary heart disease and many micro- and macrovascular diseases. CD36 is a class B scavenger receptor whose expression is prevalent in vascular lesions. It has been shown that high plasma low density lipoprotein (LDL) levels become atherogenic when oxidized to modified LDL (Ox-LDL) by inducing foam cell formation via enhanced CD36 expression on macrophages. In addition to Ox-LDL, raised levels of glucose, insulin resistance, low HDL cholesterol, increased levels of free fatty acid (FFA) all result in increased expression of CD36, thereby contributing to T2DM and related atherosclerosis. Adipocytokines such as tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), adiponectin, leptin, resistin along with peroxisome proliferator activated receptor-γ (PPAR-γ) are important mediators in glucose homeostasis in association with CD36 and can be used as markers for T2DM and atherosclerosis. Several of these gene variants have shown association with lipid metabolism, T2DM and related complications. An attempt has been made to review the CD36 macrophage receptor and related molecules in association with T2DM.

  3. Cholesterol levels in fragile X syndrome.

    Science.gov (United States)

    Berry-Kravis, Elizabeth; Levin, Rebecca; Shah, Haroon; Mathur, Shaguna; Darnell, Jennifer C; Ouyang, Bichun

    2015-02-01

    Fragile X syndrome (FXS) is associated with intellectual disability and behavioral dysfunction, including anxiety, ADHD symptoms, and autistic features. Although individuals with FXS are largely considered healthy and lifespan is not thought to be reduced, very little is known about the long-term medical health of adults with FXS and no systematically collected information is available on standard laboratory measures from metabolic screens. During the course of follow up of a large cohort of patients with FXS we noted that many patients had low cholesterol and high density lipoprotein (HDL) values and thus initiated a systematic chart review of all cholesterol values present in charts from a clinic cohort of over 500 patients with FXS. Total cholesterol (TC), low density lipoprotein (LDL) and HDL were all significantly reduced in males from the FXS cohort relative to age-adjusted population normative data. This finding has relevance for health monitoring in individuals with FXS, for treatments with cholesterol-lowering agents that have been proposed to target the underlying CNS disorder in FXS based on work in animal models, and for potential biomarker development in FXS.

  4. Perbedaan Kadar LDL-kolesterol pada Pasien Diabetes Melitus Tipe 2 dengan dan tanpa Hipertensi di RS Dr. M. Djamil Padang Tahun 2011

    Directory of Open Access Journals (Sweden)

    Finisia Noviyanti

    2015-05-01

    Full Text Available AbstrakHipertensi seringkali menjadi kondisi komorbid yang menyertai diabetes melitus tipe 2. Diabetes melitus, hipertensi dan peningkatan LDL kolesterol merupakan keadaan yang sering dijumpai saling berkaitan. Tujuan penelitian ini adalah untuk melihat perbedaan kadar LDL kolesterol penderita diabetes melitus tipe 2 dengan dan tanpa hipertensi. Penelitian ini menggunakan desain cross sectional comparatif. Pengumpulan data dilakukan dengan observasi data rekam medis pasien diabetes melitus tipe 2 dengan dan tanpa hipertensi tahun 2011 di RS. Dr. M. Djamil Padang. Analisis statistik menggunakan uji chi-square dan uji t-berpasangan. Hasil penelitian menemukan kadar LDL kolesterol pada pasien diabetes melitus tipe 2 dengan hipertensi (137,56±41,43 mg/dl lebih tinggi dibandingkan tanpa hipertensi (94,39±35,36 mg/dl. Uji chi-square menunjukkkan adanya hubungan yang bermakna antara peningkatan kadar LDL kolesterol dengan kejadian hipertensi (p<0,05. Uji t-berpasangan menunjukkan bahwa adanya perbedaan bermakna kadar LDL kolesterol antara kelompok pasien diabetes melitus dengan hipertensi dan tanpa hipertensi (p<0,05. Penelitian ini menyimpulkan adanya perbedaan yang bermakna kadar LDL kolesterol pada pasien diabetes melitus tipe 2 dengan hipertensi dan tanpa hipertensi di RS. Dr. M. Djamil Padang.Kata kunci: LDL kolesterol, diabetes melitus tipe 2, hipertensi AbstractHypertension is often a comorbid conditions that accompany diabetes mellitus type 2. Diabetes mellitus, hypertension and increased LDL cholesterol is a condition that is often be found related one another. The objective of this study was to determine difference LDL cholesterol level among diabetes melitus type 2 with hypertension and without hypertension.This research used cross-sectional comparatif design. The data was collected through observation of the patient’s medical records diabetes mellitus type 2 with hypertension and without hypertension in 2011 at the hospital Dr. M

  5. STAT5 activation induced by diabetic LDL depends on LDL glycation and occurs via src kinase activity.

    Science.gov (United States)

    Brizzi, Maria Felice; Dentelli, Patrizia; Gambino, Roberto; Cabodi, Sara; Cassader, Maurizio; Castelli, Ada; Defilippi, Paola; Pegoraro, Luigi; Pagano, Gianfranco

    2002-11-01

    Advanced glycation end products (AGEs) have been implicated in the accelerated vascular injury occurring in diabetes. We recently reported that LDL prepared from type 2 diabetic patients (dm-LDL), but not normal LDL (n-LDL) triggered signal transducers and activators of transcription STAT5 activation and p21(waf) expression in endothelial cells (ECs). The aims of the present study were to investigate the role of LDL glycation in dm-LDL- mediated signals and to analyze the molecular mechanisms leading to STAT5 activation. We found that glycated LDL (gly-LDL) triggered STAT5 activation, the formation of a prolactin inducible element (PIE)-binding complex containing STAT5, and increased p21(waf) expression through the activation of the receptor for AGE (RAGE). We also demonstrated that dm-LDL and gly-LDL, but not n-LDL treatment induced the formation of a stable complex containing the activated STAT5 and RAGE. Moreover, gly-LDL triggered src but not JAK2 kinase activity. Pretreatment with the src kinase inhibitor PP1 abrogated both STAT5 activation and the expression of p21(waf) induced by gly-LDL. Consistently, gly-LDL failed to activate STAT5 in src(-/-) fibroblasts. Collectively, our results provide evidence for the role of glycation in dm-LDL-mediated effects and for a specific role of src kinase in STAT5-dependent p21(waf) expression.

  6. What Your Cholesterol Levels Mean

    Science.gov (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More What Your Cholesterol Levels Mean Updated:Apr 3,2017 Keeping your ... content was last reviewed on 04/21/2014. Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  7. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  8. Emotional eating as a mediator between anxiety and cholesterol in population with overweight and hypertension.

    Science.gov (United States)

    Mensorio, Marinna S; Cebolla, Ausiàs; Lisón, Juan Francisco; Rodilla, Enrique; Palomar, Gonzalo; Miragall, Marta; Baños, Rosa Maria

    2016-12-23

    Although the relationship between cholesterol and mood states (especially anxiety) has been well studied, few researches have included the role of eating styles in this relationship. This study explored the associations among eating styles, negative emotional symptoms, and levels of cholesterol (and other medical variables) in a population with hypertension and overweight or obesity, analyzing the possible mediation mechanisms involved. A cross-sectional study was conducted in 68 adults with hypertension and overweight/obesity, and stepwise multiple regression analysis and mediation analyses were carried out to test the hypothesis that eating styles mediate the relationship between negative emotional symptoms and cholesterol. Several significant correlations among age, anthropometric, medical, and psychological variables (eating styles and negative emotional symptoms) were found. There was a significant indirect effect of anxiety on total cholesterol and LDL cholesterol through emotional eating. Results suggest that emotional eating has a relevant role in the rise in total and LDL cholesterol, acting as a mediator in the relationship between anxiety and cholesterol. This finding could have important implications, since it introduces a new variable in the relationship between emotions and cholesterol and, therefore, changes the way of understanding this relationship, and of treating high cholesterol in a hypertensive sample.

  9. Effects of dietary fucoxanthin on cholesterol metabolism in diabetic/obese KK-Ay mice

    Directory of Open Access Journals (Sweden)

    Beppu Fumiaki

    2012-09-01

    Full Text Available Abstract Background Fucoxanthin is a xanthophyll present in brown seaweeds and has several beneficial effects, including anti-obesity and anti-diabetic effects. However, we and another group previously observed that fucoxanthin increases serum cholesterol levels in rodents. Cholesterol is an important component of cell membranes and biosynthesis of bile acids. Serum cholesterol levels are also closely associated with atherosclerosis. Therefore, we sought to identify the mechanism underlying the increase in serum cholesterol levels by fucoxanthin. Methods Diabetic/obese KK-Ay mice were fed a diet containing 0.2% fucoxanthin for 4 weeks. The mice were sacrificed, and total blood samples were collected for the measurement of serum total cholesterol, HDL-cholesterol and non-HDL-cholesterol levels. Cholesterol content in tissues was also analyzed. Real-time PCR and Western blotting were performed to determine hepatic mRNA and protein expression of genes involved in cholesterol metabolism, respectively. Results Dietary fucoxanthin significantly increased serum HDL and non-HDL cholesterol levels, and reduced hepatic cholesterol content. In liver, the expression of SREBP1, SREBP2 and their target genes involved in cholesterol biosynthesis significantly increased and tended to increase in the fucoxanthin-fed mice, respectively. In contrast, hepatic levels of LDLR and SR-B1 proteins which is important factors for LDL-cholesterol and HDL-cholesterol uptake in the liver from serum, decreased to 60% and 80% in the fucoxanthin-fed mice, respectively, compared with the control mice. Further, we found that dietary fucoxanthin significantly increased the mRNA expression of proprotein convertase subtilisin/kexin type 9 (PCSK9, which enhances intracellular degradation of LDLR in lysosomes. Conclusions Fucoxanthin increased HDL-cholesterol and non-HDL-cholesterol levels in KK-Ay mice by inducing SREBP expression and reduced cholesterol uptake in the liver via

  10. Association of small dense lowdensity lipoprotein cholesterol in type 2 diabetics with coronary artery disease

    Directory of Open Access Journals (Sweden)

    Ya-Ching Huang

    2014-12-01

    Full Text Available Background: The risk of coronary artery disease (CAD increases two- to fourfold in diabetes. Small dense low-density lipoprotein (sdLDL particles have been linked to an increased risk for CAD. In this study, we sought to compare the sdLDL cholesterol (sdLDL-C level between the healthy control group and diabetics with CAD in the Taiwanese population. Methods: Serum specimens were collected from healthy females and males of various age groups (n = 294, type 2 diabetics (DM without complications (n = 113, and patients having DM with CAD (DM-CAD (n = 46. The commercial kit was used for the measurement of sdLDL-C level, which employs a simpler method. After heparin-magnesium precipitation of lipoproteins with density <1.044 g/ml, sdLDL (density = 1.044-1.063 g/ml remained in the supernatant and this sdLDL-C was measured using an automated chemistry analyzer. Results: The sdLDL-C level was significantly higher in males than in females (p < 0.001 and there was an age effect on sdLDL-C (p < 0.001. The DM-CAD group had significantly higher sdLDL-C levels than the healthy control group (p < 0.001, but there was no statistical difference in the LDL-C level between DM-CAD group and the healthy control group. In addition, only individuals having both high LDL-C and sdLDL-C levels had a higher risk for DM-CAD, compared to those with low LDL-C levels and low sdLDL-C levels [Odds Ratio (OR 4.97; 95% Confidence Interval (CI 1.96-12.57; p = 0.001]. Conclusions: Our data suggest that the sdLDL-C level together with the LDL-C level are better risk assessment markers for type 2 diabetics with CAD than the LDL-C level alone.

  11. Isoflavone supplementation reduces low-density lipoprotein cholesterol levels in postmenopausal women

    Directory of Open Access Journals (Sweden)

    Yenny Yenny

    2015-12-01

    Baseline subject characteristics and lipid profile in the two groups were comparable. In the isoflavone and control groups after 6 months of supplementation LDL cholesterol levels were 124.9 ± 35.2 mg/dL vs 112 .7 ± 29.7 mg/dL (p=0.013*, respectively, and after 12 months 116.9 ± 31.7 mg/dL vs 109.1 ± 29.8 mg/dL (p=0.086. There were no significant differences in the other lipid levels at 6 and 12 months. Conclusions Soy isoflavone supplementation for 6 months was capable of significantly reducing LDL cholesterol levels in postmenopausal women. No significant changes in total cholesterol, triacylgycerol, and HDL cholesterol were found after isoflavone supplementation.

  12. Lysosomal acid lipase: At the crossroads of normal and atherogenic cholesterol metabolism

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    Joshua A Dubland

    2015-02-01

    Full Text Available Unregulated cellular uptake of apolipoprotein B-containing lipoproteins in the arterial intima leads to the formation of foam cells in atherosclerosis. Lysosomal acid lipase (LAL plays a crucial role in both lipoprotein lipid catabolism and excess lipid accumulation as it is the primary enzyme that hydrolyzes cholesteryl esters derived from both low density lipoprotein (LDL and modified forms of LDL. Evidence suggests that as atherosclerosis progresses, accumulation of excess free cholesterol in lysosomes leads to impairment of LAL activity, resulting in accumulation of cholesteryl esters in the lysosome as well as the cytosol in foam cells. Impaired metabolism and release of cholesterol from lysosomes can lead to downstream defects in ATP-binding cassette transporter A1 regulation, needed to offload excess cholesterol from plaque foam cells. This review focuses on the role LAL plays in normal cholesterol metabolism and how the associated changes in its enzymatic activity may ultimately contribute to atherosclerosis progression.

  13. Synthetic High-Density Lipoprotein-Like Nanocarrier Improved Cellular Transport of Lysosomal Cholesterol in Human Sterol Carrier Protein-Deficient Fibroblasts.

    Science.gov (United States)

    Nam, Da-Eun; Kim, Ok-Kyung; Park, Yoo Kyoung; Lee, Jeongmin

    2016-01-01

    Sterol carrier protein-2 (SCP-2), which is not found in tissues of people with Zellweger syndrome, facilitates the movement of cholesterol within cells, resulting in abnormal accumulation of cholesterol in SCP-2-deficient cells. This study investigated whether synthetic high-density lipoprotein-like nanocarrier (sHDL-NC) improves the cellular transport of lysosomal cholesterol to plasma membrane in SCP-2-deficient fibroblasts. Human SCP-2-deficient fibroblasts were incubated with [(3)H-cholesterol]LDL as a source of cholesterol and sHDL-NC. The cells were fractionated by centrifugation permit tracking of [(3)H]-cholesterol from lysosome into plasma membrane. Furthermore, cellular content of cholesteryl ester as a storage form and mRNA expression of low-density lipoprotein (LDL) receptor were measured to support the cholesterol transport to plasma membrane. Incubation with sHDL-NC for 8 h significantly increased uptake of [(3)H]-cholesterol to lysosome by 53% and further enhanced the transport of [(3)H]-cholesterol to plasma membrane by 32%. Treatment with sHDL-NC significantly reduced cellular content of cholesteryl ester and increased mRNA expression of LDL receptor (LDL-R). In conclusion, sHDL-NC enables increased transport of lysosomal cholesterol to plasma membrane. In addition, these data were indirectly supported by decreased cellular content of cholesteryl ester and increased gene expression of LDL-R. Therefore, sHDL-NC may be a useful vehicle for transporting cholesterol, which may help to prevent accumulation of cholesterol in SCP-2-deficient fibroblasts.

  14. Observational study of lipid profile and LDL particle size in patients with metabolic syndrome

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    Martínez-Mernández Pedro

    2011-09-01

    Full Text Available Abstract Background The atherogenic lipoprotein phenotype is characterized by an increase in plasma triglycerides, a decrease in high-density lipoprotein cholesterol (HDLc, and the prevalence of small, dense-low density lipoprotein cholesterol (LDLc particles. The aim of this study was to establish the importance of LDL particle size measurement by gender in a group of patients with Metabolic Syndrome (MS attending at a Cardiovascular Risk Unit in Primary Care and their classification into phenotypes. Subjects and methods One hundred eighty-five patients (93 men and 92 women from several areas in the South of Spain, for a period of one year in a health centre were studied. Laboratory parameters included plasma lipids, lipoproteins, low-density lipoprotein size and several atherogenic rates were determinated. Results We found differences by gender between anthropometric parameters, blood pressure and glucose measures by MS status. Lipid profile was different in our two study groups, and gender differences in these parameters within each group were also remarkable, in HDLc and Apo A-I values. According to LDL particle size, we found males had smaller size than females, and patients with MS had also smaller than those without MS. We observed inverse relationship between LDL particle size and triglycerides in patients with and without MS, and the same relationship between all atherogenic rates in non-MS patients. When we considered our population in two classes of phenotypes, lipid profile was worse in phenotype B. Conclusion In conclusion, we consider worthy the measurement of LDL particle size due to its relationship with lipid profile and cardiovascular risk.

  15. High levels of LDL-C combined with low levels of HDL-C further increase platelet activation in hypercholesterolemic patients.

    Science.gov (United States)

    Chan, L W; Luo, X P; Ni, H C; Shi, H M; Liu, L; Wen, Z C; Gu, X Y; Qiao, J; Li, J

    2015-02-01

    High levels of low-density lipoprotein cholesterol (LDL-C) enhance platelet activation, whereas high levels of high-density lipoprotein cholesterol (HDL-C) exert a cardioprotective effect. However, the effects on platelet activation of high levels of LDL-C combined with low levels of HDL-C (HLC) have not yet been reported. We aimed to evaluate the platelet activation marker of HLC patients and investigate the antiplatelet effect of atorvastatin on this population. Forty-eight patients with high levels of LDL-C were enrolled. Among these, 23 had HLC and the other 25 had high levels of LDL-C combined with normal levels of HDL-C (HNC). A total of 35 normocholesterolemic (NOMC) volunteers were included as controls. Whole blood flow cytometry and platelet aggregation measurements were performed on all participants to detect the following platelet activation markers: CD62p (P-selectin), PAC-1 (GPIIb/IIIa), and maximal platelet aggregation (MPAG). A daily dose of 20 mg atorvastatin was administered to patients with high levels of LDL-C, and the above assessments were obtained at baseline and after 1 and 2 months of treatment. The expression of platelets CD62p and PAC-1 was increased in HNC patients compared to NOMC volunteers (PHDL-C further increased platelet activation in patients with high levels of LDL-C. Platelet activation remained higher among HLC patients regardless of atorvastatin treatment.

  16. High serum total cholesterol--an indicator for monitoring cholesterol lowering efforts: U.S. adults, 2005-2006.

    Science.gov (United States)

    Schober, Susan E; Carroll, Margaret D; Lacher, David A; Hirsch, Rosemarie

    2007-12-01

    Elevated serum total cholesterol is a major and modifiable risk factor for heart disease, the lead-ing cause of death in the United States (1,2). Reducing mean total serum cholesterol levels among adults to less than 200 mg/dL and reducing the proportion who have levels of 240 mg/dL or higher to less than 17% are national Healthy People 2010 objectives (3). Age-adjusted mean serum cholesterol levels among adults aged 20-74 years declined from 222 mg/dL in 1960-1962 to 203 mg/dL in 1999-2002 (4). Among adults aged 20 years and older, the percent of the population with high serum total cholesterol levels (240 mg/dL or higher) declined from 20% during 1988-1994 to 17% during 1999-2002 (4). In individual patients, a high serum total cholesterol level indicates a potential increased risk for heart disease, but further evaluation of other risk factors and the specific components of cholesterol provide the basis for determining the need for initiating therapeutic lifestyle changes or treatment with medication (5). Low-density-lipoprotein (LDL) is the cholesterol component associated with arterial blockage, and it is the primary clinical target for cholesterol management. High-density-lipoprotein (HDL) may help to protect individuals from developing heart disease. In populations, comparisons of total cholesterol levels over time can show if population groups are experiencing improvement in cholesterol levels, and knowledge of trends in levels of total cholesterol can help identify subgroups where additional prevention efforts may be needed.

  17. Paradoxical Negative HDL Cholesterol Response to Atorvastatin and Simvastatin Treatment in Chinese Type 2 Diabetic Patients

    OpenAIRE

    Chang, Yu-Hung; Lin, Kun-Cheng; Chang, Dao-Ming; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

    2013-01-01

    OBJECTIVES: There is extensive but controversial evidence on the diverse effects of statins on the level of high-density lipoprotein cholesterol (HDL-C). Some of these effects may limit the benefits of statins in terms of cardiovascular risk reduction. To identify the conditions for beneficial effects, this study investigated the response to atorvastatin and simvastatin treatment in type 2 diabetic patients with elevated low-density lipoprotein cholesterol (LDL-C). METHODS: 2,872 subjects wit...

  18. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

    Science.gov (United States)

    Marshall, Stephanie M; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; McDaniel, Allison L; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

    2014-01-01

    An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

  19. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

    Full Text Available An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL support TICE, antisense oligonucleotides (ASO were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP, which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg mice, which predominantly excrete cholesterol via TICE, and wild type (WT littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

  20. Traffic air pollution and oxidized LDL.

    Directory of Open Access Journals (Sweden)

    Lotte Jacobs

    Full Text Available BACKGROUND: Epidemiologic studies indirectly suggest that air pollution accelerates atherosclerosis. We hypothesized that individual exposure to particulate matter (PM derived from fossil fuel would correlate with plasma concentrations of oxidized low-density lipoprotein (LDL, taken as a marker of atherosclerosis. We tested this hypothesis in patients with diabetes, who are at high risk for atherosclerosis. METHODOLOGY/PRINCIPAL FINDINGS: In a cross-sectional study of non-smoking adult outpatients with diabetes we assessed individual chronic exposure to PM by measuring the area occupied by carbon in airway macrophages, collected by sputum induction and by determining the distance from the patient's residence to a major road, through geocoding. These exposure indices were regressed against plasma concentrations of oxidized LDL, von Willebrand factor and plasminogen activator inhibitor 1 (PAI-1. We could assess the carbon load of airway macrophages in 79 subjects (58 percent. Each doubling in the distance of residence from major roads was associated with a 0.027 µm(2 decrease (95% confidence interval (CI: -0.048 to -0.0051 in the carbon load of airway macrophages. Independently from other covariates, we found that each increase of 0.25 µm(2 [interquartile range (IQR] in carbon load was associated with an increase of 7.3 U/L (95% CI: 1.3 to 13.3 in plasma oxidized LDL. Each doubling in distance of residence from major roads was associated with a decrease of -2.9 U/L (95% CI: -5.2 to -0.72 in oxidized LDL. Neither the carbon load of macrophages nor the distance from residence to major roads, were associated with plasma von Willebrand factor or PAI-1. CONCLUSIONS: The observed positive association, in a susceptible group of the general population, between plasma oxidized LDL levels and either the carbon load of airway macrophages or the proximity of the subject's residence to busy roads suggests a proatherogenic effect of traffic air pollution.

  1. Evolocumab lowers LDL-C safely and effectively when self-administered in the at-home setting

    OpenAIRE

    Dent,Ricardo; Joshi, Raju; Stephen Djedjos, C.; Legg, Jason; Elliott, Mary; Geller, Michelle; Meyer, Dawn; Somaratne, Ransi; Recknor, Chris; Weiss, Robert

    2016-01-01

    Evolocumab has been shown to consistently reduce low-density lipoprotein cholesterol (LDL-C) across populations. The phase 3 studies included administration in the home-use and in-clinic settings but did not specifically evaluate the feasibility of home-use administration. Two clinical studies enrolled patients with hypercholesterolemia or mixed dyslipidemia on statin therapy and with/without ezetimibe received evolocumab in the home-use setting. Patients were randomized to self-administer ev...

  2. Sesamin Enhances Cholesterol Efflux in RAW264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Nan Liu

    2014-06-01

    Full Text Available Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL in RAW264.7 cells. Treatment with sesamin (10 μM significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL. Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

  3. Sesamin enhances cholesterol efflux in RAW264.7 macrophages.

    Science.gov (United States)

    Liu, Nan; Wu, Chongming; Sun, Lizhong; Zheng, Jun; Guo, Peng

    2014-06-06

    Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 μM) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

  4. Macrophage cholesterol homeostasis and metabolic diseases: critical role of cholesteryl ester mobilization.

    Science.gov (United States)

    Ghosh, Shobha

    2011-03-01

    Atherogenic dyslipidemia, including low HDL levels, is the major contributor of residual risk of cardiovascular disease that remains even after aggressive statin therapy to reduce LDL-cholesterol. Currently, distinction is not made between HDL-cholesterol and HDL, which is a lipoprotein consisting of several proteins and a core containing cholesteryl esters (CEs). The importance of assessing HDL functionality, specifically its role in facilitating cholesterol efflux from foam cells, is relevant to atherogenesis. Since HDLs can only remove unesterified cholesterol from macrophages while cholesterol is stored as CEs within foam cells, intracellular CE hydrolysis by CE hydrolase is vital. Reduction in macrophage lipid burden not only attenuates atherosclerosis but also reduces inflammation and linked pathologies such as Type 2 diabetes and chronic kidney disease. Targeting reduction in macrophage CE levels and focusing on enhancing cholesterol flux from peripheral tissues to liver for final elimination is proposed.

  5. Regulation of cholesterol homeostasis.

    Science.gov (United States)

    van der Wulp, Mariëtte Y M; Verkade, Henkjan J; Groen, Albert K

    2013-04-10

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia.

  6. A Decreased Responsiveness of Platelet to Nitric Oxide in Cholesterol-Fed Rabbits

    Institute of Scientific and Technical Information of China (English)

    SUNJing; ZHANGAi-xia; LUOChun-xia; WANGWei; SUNYong-jun; ZHUDong-ya

    2004-01-01

    To determine whether endothelial dysfunction leads to an abnormal responsiveness of platelet to nitric oxide(NO)during the development of atherosclerosis. Methods:Rabbits were fed a 1% cholesterol chow for 12 weeks to induce atherosclerosis. Sermn NOx levels and the responsiveness of platelet to NO donor SNP were determined every 4 weeks during maintaining on a chow containing 1% cholesterol. The measurement of serum lipids and the examination of morphological feature and endothelial-dependent relaxation of aorta were performed after 12 weeks of cholesterol diet. Resu/ts.Cholesterol diet significantly increased sermn levels of cholesterol and LDL, caused a remarkable platelet hyperaggregability, and produced an evident endothelial dysfunction as indicated by the diminished vasorelaxation induced by acetylcholine and endothelial cell lesion as exhibited by scanning electron microscope examination. The percentage of inhibition of ADP-induced platelet aggregation by NO donor SNIP was significantly smaller in cholesterol chow group than that in normal chow group although no significant difference in serum NOx levels between normal and cholesterol chow group was observed throughout the development of atherosclexosis. :The present study suggests that the endothelial dysfunction caused by enhanced sermn cholesterol and LDL levels induces a decreased responsiveness of platelet to NO.

  7. The plasma concentration of HDL-associated apoM is influenced by LDL receptor-mediated clearance of apoB-containing particles.

    Science.gov (United States)

    Christoffersen, Christina; Benn, Marianne; Christensen, Pernille M; Gordts, Philip L S M; Roebroek, Anton J M; Frikke-Schmidt, Ruth; Tybjaerg-Hansen, Anne; Dahlbäck, Björn; Nielsen, Lars B

    2012-10-01

    ApoM is mainly associated with HDL. Nevertheless, we have consistently observed positive correlations of apoM with plasma LDL cholesterol in humans. Moreover, LDL receptor deficiency is associated with increased plasma apoM in mice. Here, we tested the idea that plasma apoM concentrations are affected by the rate of LDL receptor-mediated clearance of apoB-containing particles. We measured apoM in humans each carrying one of three different LDL receptor mutations (n = 9) or the apoB3500 mutation (n = 12). These carriers had increased plasma apoM (1.34 ± 0.13 µM, P = 0.003, and 1.23 ± 0.10 µM, P = 0.02, respectively) as compared with noncarriers (0.93 ± 0.04 µM). When we injected human apoM-containing HDL into Wt (n = 6) or LDL receptor-deficient mice (n = 6), the removal of HDL-associated human apoM was delayed in the LDL receptor-deficient mice. After 2 h, 54 ± 5% versus 90 ± 8% (P LDL receptor-deficient mice, respectively. Finally, we compared the turnover of radio-iodinated LDL and plasma apoM concentrations in 45 normocholesterolemic humans. There was a negative correlation between plasma apoM and the fractional catabolic rate of LDL (r = -0.38, P = 0.009). These data suggest that the plasma clearance of apoM, despite apoM primarily being associated with HDL, is influenced by LDL receptor-mediated clearance of apoB-containing particles.

  8. blood HDL-cholesterol concentrations (ID 1747, 1748, 1864, 1951, 1954, 4693) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    claims in relation to policosanols from sugar cane wax and maintenance of normal blood LDL-cholesterol concentrations and maintenance of normal blood HDL-cholesterol concentrations. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article...

  9. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys.

    Science.gov (United States)

    Dong, Qiao-Xiang; Rodenburg, Sarah E; Hill, Dana; Vandevoort, Catherine A

    2011-05-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  10. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys

    Institute of Scientific and Technical Information of China (English)

    Qiao-Xiang Dong; Sarah E Rodenburg; Dana Hill; Catherine A VandeVoort

    2011-01-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  11. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol.

    Science.gov (United States)

    Della Badia, Laura A; Elshourbagy, Nabil A; Mousa, Shaker A

    2016-08-01

    Statins and other lipid-lowering drugs have dominated the market for many years for achievement of recommended levels of low-density lipoprotein cholesterol (LDL-C). However, a substantial number of high-risk patients are unable to achieve the LDL-C goal. Proprotein convertase subtilisin/kexin 9 (PCSK9) has recently emerged as a new, promising key therapeutic target for hypercholesterolemia. PCSK9 is a protease involved in chaperoning the low-density lipoprotein receptor to the process of degradation. PCSK9 inhibitors and statins effectively lower LDL-C. The PCSK9 inhibitors decrease the degradation of the LDL receptors, whereas statins mainly interfere with the synthetic machinery of cholesterol by inhibiting the key rate limiting enzyme, the HMG CoA reductase. PCSK9 inhibitors are currently being developed as monoclonal antibodies for their primary use in lowering LDL-C. They may be especially useful for patients with homozygous familial hypercholesterolemia, who at present receive minimal benefit from traditional statin therapy. The monoclonal antibody PCSK9 inhibitors, recently granted FDA approval, show the most promising safety and efficacy profile compared to other, newer LDL-C lowering therapies. This review will primarily focus on the safety and efficacy of monoclonal antibody PCSK9 inhibitors in comparison to statins. The review will also address new, alternative PCSK9 targeting drug classes such as small molecules, gene silencing agents, apolipoprotein B antisense oligonucleotides, and microsomal triglyceride transfer protein inhibitors.

  12. Effect of yogurt and bifidus yogurt fortified with skim milk powder, condensed whey and lactose-hydrolysed condensed whey on serum cholesterol and triacylglycerol levels in rats.

    Science.gov (United States)

    Beena, A; Prasad, V

    1997-08-01

    The possible hypocholesterolaemic properties of milk and fermented milk products have been investigated in groups of albino rats given a basal diet, basal diet plus cholesterol, and basal diet plus cholesterol together with whole milk or standard or bifidus yogurt. The yogurts were fortified with skim milk powder, condensed whey or lactose-hydrolysed condensed whey. After 30 d, triacylglycerols, total cholesterol, HDL-cholesterol and LDL-cholesterol were measured in serum. Whole milk and ordinary yogurt had no hypocholesterolaemic effect, but standard yogurt containing lactose-hydrolysed condensed whey and all bifidus yogurts lowered serum cholesterol. In general, yogurts changed HDL-cholesterol little, but tended to raise triacylglycerols. There was marked lowering of LDL-cholesterol in rats given either type of yogurt fortified with whey proteins. This study has demonstrated in a rat model that bifidus yogurts and yogurts fortified with whey proteins can reduce total and LDL-cholesterol, and suggests that if they have the same effect in human subjects they have potential value in cholesterol-lowering diets.

  13. The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism

    NARCIS (Netherlands)

    Demetz, Egon; Schroll, Andrea; Auer, Kristina; Heim, Christiane; Patsch, Josef R.; Eller, Philipp; Theurl, Markus; Theurl, Igor; Theurl, Milan; Seifert, Markus; Lener, Daniela; Stanzl, Ursula; Haschka, David; Asshoff, Malte; Dichtl, Stefanie; Nairz, Manfred; Huber, Eva; Stadlinger, Martin; Moschen, Alexander R.; Li, Xiaorong; Pallweber, Petra; Scharnagl, Hubert; Stojakovic, Tatjana; Maerz, Winfried; Kleber, Marcus E.; Garlaschelli, Katia; Uboldi, Patrizia; Catapano, Alberico L.; Stellaard, Frans; Rudling, Mats; Kuba, Keiji; Imai, Yumiko; Arita, Makoto; Schuetz, John D.; Pramstaller, Peter P.; Tietge, Uwe J. F.; Trauner, Michael; Norata, Giuseppe D.; Claudel, Thierry; Hicks, Andrew A.; Weiss, Guenter; Tancevski, Ivan

    2014-01-01

    Cholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By co

  14. Direct Low Density Lipoprotein Cholesterol and Glycated Albumin 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) have been associated with a decreased risk of these complications. The aim in this st...

  15. 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...

  16. ABC-transporters and lipid transfer proteins : important players in macrophage cholesterol homeostasis and atherosclerosis

    NARCIS (Netherlands)

    Ye, Dan

    2008-01-01

    Local modulation of macrophage cholesterol metabolism in the arterial wall and systemic regulation of lipoprotein metabolism (LDL-lowering and/or HDL-raising) are both attractive targets for future drug design for the prevention of atherosclerosis. As described in this thesis, bone marrow transplant

  17. The cholesterol-raising factor from boiled coffee does not pass a paper filter.

    NARCIS (Netherlands)

    Dusseldorp, van M.; Katan, M.B.; Vliet, van T.; Demacker, P.N.M.; Stalenhoef, A.F.H.

    1991-01-01

    Previous studies have indicated that consumption of boiled coffee raises total and low density lipoprotein (LDL) cholesterol, whereas drip-filtered coffee does not. We have tested the effect on serum lipids of consumed coffee that was first boiled and then filtered through commercial paper coffee fi

  18. 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.

  19. Cholesterol-lowering activity of soy-derived glyceollins in the golden Syrian hamster model.

    Science.gov (United States)

    Huang, Haiqiu; Xie, Zhuohong; Boue, Stephen M; Bhatnagar, Deepak; Yokoyama, Wallace; Yu, Liangli Lucy; Wang, Thomas T Y

    2013-06-19

    Hypercholesterolemia is one of the major factors contributing to the risk of cardiovascular disease (CVD), which is the leading cause of death in developed countries. Consumption of soy foods has been recognized to lower the risk of CVD, and phytochemicals in soy are believed to contribute to the health benefits. Glyceollin is one of the candidate phytochemicals synthesized in stressed soy that may account for many unique biological activities. In this study, the in vivo cholesterol-lowering effect of glyceollins was investigated. Male golden Syrian hamsters were fed diets including (1) 36 kcal% fat diet, (2) 36 kcal% fat diet containing 250 mg/kg diet glyceollins, or (3) chow for 28 days. Hepatic cholesterol esters and free cholesterol, hepatic total lipid content, plasma lipoproteins, fecal bile acid, fecal total cholesterol, and cholesterol metabolism related gene expressions were measured. Glyceollin supplementation led to significant reduction of plasma VLDL, hepatic cholesterol esters, and total lipid content. Consistent with changes in circulating cholesterol, glyceollin supplementation also altered expression of the genes related to cholesterol metabolism in the liver. In contrast, no change in plasma LDL and HDL, fecal bile acid, or cholesterol content was observed. The cholesterol-lowering effect of glyceollins appeared not to go through the increase of bile excretion. These results supported glyceollins' role as novel soy-derived cholesterol-lowering phytochemicals that may contribute to soy's health effects.

  20. 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.

  1. Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.; (UTSMC)

    2010-09-21

    LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

  2. Cholesterol concentration in seminal plasma as a predictive tool for quality semen evaluation.

    Science.gov (United States)

    Beer-Ljubić, B; Aladrović, J; Marenjak, T S; Laskaj, R; Majić-Balić, I; Milinković-Tur, S

    2009-11-01

    The aim of this study was to investigate the relationship between lipid composition of bovine serum and seminal plasma, seasonality, and semen quality. The experiment was carried out in two groups of Simmental breeding bulls: Group I (ages 2 to 4 yr) and Group II (ages 5 to 10 yr). Blood samples were collected from jugular vein, and bovine semen was sampled with an artificial vagina once per season. Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triacylglycerols, nonesterified fatty acids (NEFAs), and lipoprotein electrophoretic patterns were determined. Seminal plasma concentrations of total cholesterol, HDL-C, and LDL-C were assayed. Serum concentration of triacylglycerols in young bulls was significantly higher in winter compared with that in autumn, whereas serum NEFA concentration was significantly higher in autumn compared with that in other seasons. Serum concentration of total cholesterol, LDL-C, and LDL lipoproteins in older bulls was significantly higher in winter than in spring. Seminal plasma concentration of total cholesterol in young bulls was significantly higher in spring compared with that in summer, whereas in older bulls it was significantly higher in winter compared with that in autumn samples. Sperm volume of both groups was significantly higher in summer compared with that in autumn and winter. Sperm motility in young bulls was lowest in summer and differed significantly from the values recorded in other seasons. The changes observed in seminal plasma cholesterol concentration were associated with extracellular lipid use and appeared to be applicable as a biochemical marker of sperm quality.

  3. Replication of LDL GWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

    LENUS (Irish Health Repository)

    Trompet, Stella

    2011-10-06

    Abstract Background The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER\\/PHASE project and second show that the PROSPER\\/PHASE study can be used to study pharmacogenetics in the elderly. Methods The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer\\'s instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification. Results Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE\\/APOC1; LDLR; FADS2\\/FEN1; HMGCR; PSRC1\\/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results. Conclusion With the GWAS in the PROSPER\\/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof

  4. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  5. Apolipoprotein E competitively inhibits receptor-dependent low density lipoprotein uptake by the liver but has no effect on cholesterol absorption or synthesis in the mouse.

    Science.gov (United States)

    Woollett, L A; Osono, Y; Herz, J; Dietschy, J M

    1995-01-01

    This study examines the question of whether apolipoprotein E (apoE) alters steady-state concentrations of plasma cholesterol carried in low density lipoproteins (LDL-C) by acting as a competitive inhibitor of hepatic LDL uptake or by altering the rate of net cholesterol delivery from the intestinal lumen to the liver. To differentiate between these two possibilities, rates of cholesterol absorption and synthesis and the kinetics of hepatic LDL-C transport were measured in vivo in mice with either normal (apoE+/+) or zero (apoE-/-) levels of circulating apoE. Rates of cholesterol absorption were essentially identical in both genotypes and equaled approximately 44% of the daily dietary load of cholesterol. This finding was consistent with the further observation that the rates of cholesterol synthesis in the liver (approximately 2,000 nmol/h) and extrahepatic tissues (approximately 3,000 nmol/h) were also essentially identical in the two groups of mice. However, the apparent Michaelis constant for receptor-dependent hepatic LDL-C uptake was markedly lower in the apoE-/- mice (44 +/- 4 mg/dl) than in the apoE+/+ animals (329 +/- 77 mg/dl) even though the maximal transport velocity for this uptake process was essentially the same (approximately 400 micrograms/h per g) in the two groups of mice. These studies, therefore, demonstrate that apoE-containing lipoproteins can act as potent competitive inhibitors of hepatic LDL-C transport and so can significantly increase steady-state plasma LDL-C levels. This apolipoprotein plays no role, however, in the regulation of cholesterol absorption, sterol biosynthesis, or hepatic LDL receptor number, at least in the mouse. PMID:8618929

  6. Cheese intake lowers plasma cholesterol concentrations without increasing bile acid excretion

    DEFF Research Database (Denmark)

    Hjerpsted, Julie Bousgaard; Dragsted, Lars Ove; Tholstrup, Tine

    2016-01-01

    Purpose Cheese is a dairy product with high calcium content. It has been suggested that calcium intake may increase fecal excretion of bile acids that would cause a regeneration of bile acids from hepatic cholesterol and thereby result in a lowering of plasma cholesterol concentrations. We aimed...... with 13% energy from cheese or butter. Results After 6 weeks of intervention cheese resulted in higher amounts of calcium excreted in feces compared to butter. However, no difference was observed in fecal bile acid output despite lower serum total, LDL and HDL cholesterol concentrations observed...

  7. Low HDL cholesterol, aggression and altered central serotonergic activity.

    Science.gov (United States)

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  8. Prevalence and characteristics of patients with low levels of low-density lipoprotein cholesterol in northern Denmark: a descriptive study

    Directory of Open Access Journals (Sweden)

    Schmidt SA

    2015-02-01

    Full Text Available Sigrun Alba Johannesdottir Schmidt,1 Uffe Heide-Jørgensen,1 Angelika D Manthripragada,2 Vera Ehrenstein1 1Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 2Center for Observational Research, Amgen Inc., Thousand Oaks, CA, USA Background: With the emergence of new lipid-lowering therapies, more patients are expected to achieve substantial lowering of low-density lipoprotein cholesterol (LDL-C. However, there are limited data examining the clinical experience of patients with low (<1.3 mmol/L or very low (<0.65 mmol/L levels of LDL-C. To provide information on patients with low LDL-C, we identified and characterized persons with low LDL-C using data from Danish medical databases. Methods: Using a population-based clinical laboratory database, we identified adults with at least one LDL-C measurement in northern Denmark between 1998 and 2011 (population approximately 1.5 million persons. Based on the lowest measurement during the study period, we divided patients into groups with low (<1.3 mmol/L, moderate (1.3–3.3 mmol/L, or high (>3.3 mmol/L LDL-C. We described their demographic characteristics, entire comorbidity history, and 90-day prescription history prior to the lowest LDL-C value measured. Finally, we further restricted the analysis to individuals with very low LDL-C (<0.65 mmol/L. Results: Among 765,503 persons with an LDL-C measurement, 23% had high LDL-C, 73% had moderate LDL-C, and 4.8% had low LDL-C. In the latter group, 9.6% (0.46% of total had very low LDL-C. Compared with the moderate and high LDL-C categories, the low LDL-C group included more males and older persons with a higher prevalence of cardiovascular disease, diabetes, chronic pulmonary disease, ulcer disease, and obesity, as measured by hospital diagnoses or relevant prescription drugs for these diseases. Cancer and use of psychotropic drugs were also more prevalent. These patterns of distribution became even more pronounced when

  9. Polyacrylate adsorbents for the selective adsorption of cholesterol-rich lipoproteins from plasma or blood

    Directory of Open Access Journals (Sweden)

    Heuck, Claus-Chr.

    2011-01-01

    Full Text Available Polyacrylate (PAA adsorbents selectively bind low density lipoproteins (LDL from human plasma and blood, whereas very low density lipoproteins (VLDL are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw of the polyanion ligand. Ca++ and Mg++ inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL are repelled from the adsorbents due to their higher negative surface charge density.

  10. Polyacrylate adsorbents for the selective adsorption of cholesterol-rich lipoproteins from plasma or blood.

    Science.gov (United States)

    Heuck, Claus-Chr

    2011-01-24

    Polyacrylate (PAA) adsorbents selectively bind low density lipoproteins (LDL) from human plasma and blood, whereas very low density lipoproteins (VLDL) are only minimally adsorbed. The adsorption of cholesterol-rich lipoproteins to PAA adsorbents is related to the molecular weight (mw) of the polyanion ligand. Ca(++) and Mg(++) inhibit the binding of LDL to PAA adsorbents. The chemical composition of the organic hardgels of the adsorbents does not have an influence on adsorption. The selective adsorption of LDL to PAA adsorbents can be explained to result from their low negative surface charge density and the specific colloid-chemical properties of the surface-bound PAA, which do not prevent LDL from binding to charge-like domains of the ligand. By contrast, VLDL and high density lipoproteins (HDL) are repelled from the adsorbents due to their higher negative surface charge density.

  11. Optimization of LDL targeted nanostructured lipid carriers of 5-FU by a full factorial design

    Directory of Open Access Journals (Sweden)

    Sare Andalib

    2012-01-01

    Full Text Available Background: Nanostructured lipid carriers (NLC are a mixture of solid and liquid lipids or oils as colloidal carrier systems that lead to an imperfect matrix structure with high ability for loading water soluble drugs. The aim of this study was to find the best proportion of liquid and solid lipids of different types for optimization of the production of LDL targeted NLCs used in carrying 5-Fu by the emulsification-solvent evaporation method. Materials and Methods: The influence of the lipid type, cholesterol or cholesteryl stearate for targeting LDL receptors, oil type (oleic acid or octanol, lipid and oil% on particle size, surface charge, drug loading efficiency, and drug released percent from the NLCs were studied by a full factorial design. Results: The NLCs prepared by 54.5% cholesterol and 25% of oleic acid, showed optimum results with particle size of 105.8 nm, relatively high zeta potential of −25 mV, drug loading efficiency of 38% and release efficiency of about 40%. Scanning electron microscopy of nanoparticles confirmed the results of dynamic light scattering method used in measuring the particle size of NLCs. Conclusions: The optimization method by a full factorial statistical design is a useful optimization method for production of nanostructured lipid carriers.

  12. What Causes High Blood Cholesterol?

    Science.gov (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  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. Elevated levels of serum cholesterol are associated with better performance on tasks of episodic memory.

    Science.gov (United States)

    Leritz, Elizabeth C; McGlinchey, Regina E; Salat, David H; Milberg, William P

    2016-04-01

    We examined how serum cholesterol, an established risk factor for cerebrovascular disease (CVD), relates to cognitive function in healthy middle-older aged individuals with no neurologic or CVD history. A complete lipid panel was obtained from a cohort of one hundred twenty individuals, ages 43-85, who also underwent a comprehensive neuropsychological examination. In order to reduce the number of variables and empirically identify broad cognitive domains, scores from neuropsychological tests were submitted into a factor analysis. This analysis revealed three explainable factors: Memory, Executive Function and Memory/Language. Three separate hierarchical multiple regression analyses were conducted using individual cholesterol metrics (total cholesterol, low density lipoprotein; LDL, high density lipoprotein; HDL, and triglycerides), as well as age, education, medication status (lipid lowering agents), ApoE status, and additional risk factors for CVD to predict neuropsychological function. The Memory Factor was predicted by a combination of age, LDL, and triglyceride levels; both age and triglycerides were negatively associated with factor score, while LDL levels revealed a positive relationship. Both the Executive and Memory/Language factor were only explained by education, whereby more years were associated with better performance. These results provide evidence that individual cholesterol lipoproteins and triglycerides may differentially impact cognitive function, over and above other common CVD risk factors and ApoE status. Our findings demonstrate the importance of consideration of vascular risk factors, such as cholesterol, in studies of cognitive aging.

  15. Role of cholesterol 7alpha-hydroxylase (CYP7A1) in nutrigenetics and pharmacogenetics of cholesterol lowering.

    Science.gov (United States)

    Hubacek, Jaroslav A; Bobkova, Dagmar

    2006-01-01

    The relationship between dietary composition/cholesterol-lowering therapy and final plasma lipid levels is to some extent genetically determined. It is clear that these responses are under polygenic control, with multiple variants in many genes participating in the total effect (and with each gene contributing a relatively small effect). Using different experimental approaches, several candidate genes have been analyzed to date.Interesting and consistent results have been published recently regarding the A-204C promoter variant in the cholesterol 7alpha-hydroxylase (CYP7A1) gene. CYP7A1 is a rate-limiting enzyme in bile acid synthesis and therefore plays an important role in maintaining cholesterol homeostasis. CYP7A1-204CC homozygotes have the greatest decrease in total cholesterol level in response to dietary changes in different types of dietary intervention studies. In contrast, one study has reported that the effect of statins in lowering low-density lipoprotein (LDL)-cholesterol levels was slightly greater in -204AA homozygotes. The CYP7A1 A-204C variant accounts for a significant proportion of the genetic predisposition of the response of plasma cholesterol levels.

  16. Is the Ratio of Antibodies Against Oxidized LDL to Oxidized LDL an Indicator of Cardiovascular Risk in Psoriasis?

    Directory of Open Access Journals (Sweden)

    Medha Rajappa

    2016-09-01

    Full Text Available Objectives: Psoriasis is a chronic inflammatory skin disease. Chronic inflammation results in increased oxidative stress and oxidizes lipoproteins, increasing their atherogenicity. This study sought to estimate the levels of oxidized low-density lipoprotein (ox-LDL and antibodies against oxidized LDL (anti-ox-LDL and compute the ratio of anti-ox-LDL/ox-LDL as a single composite parameter to assess the oxidative lipoprotein burden as an indicator of cardiovascular risk in patients with psoriasis. Methods: This cross-sectional study included 45 patients with psoriasis. All patients were given a psoriasis severity index score and their ox-LDL and anti-ox-LDL estimated using ELISA. Results: The results of this study show an elevation in the ratio of anti-ox-LDL to ox-LDL in patients with psoriasis, which initiate and perpetuate the pathogenesis of psoriasis and its comorbidity, atherosclerotic cardiovascular disease. Conclusions: Our results suggest that an elevated ratio of anti-ox-LDL/ox-LDL can serve as a composite parameter reflecting the total oxidative lipoprotein burden and cardiovascular risk in psoriasis patients.

  17. The Effects of Jiang-Zhi-Ning and Its Main Components on Cholesterol Metabolism

    Directory of Open Access Journals (Sweden)

    Jianxin Chen

    2012-01-01

    Full Text Available To examine how Jiang-Zhi-Ning (JZN regulates cholesterol metabolism and compare the role of its four main components. We established a beagle model of hyperlipidemia, fed with JZN extract and collected JZN-containing serum 0, 1, 2, 4, and 6 h later. Human liver cells Bel-7402 were stimulated with 10% JZN-containing serum as well as the four main components of JZN and Atorvastatin. The mRNA expression of LDL receptor (LDL-R, 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR, cytochrome P450 7A1 (CYP7A1, and acetyl-Coenzyme A acetyltransferase 2 (ACAT2 was measured by real-time PCR. LDL-R surface expression and LDL-binding and internalization were examined by flow cytometry. The results showed that JZN-containing serum significantly increased the mRNA expression of LDL-R, HMG-CoAR, and CYP7A1 in Bel-7402 cells. All the four components significantly increased the mRNA and protein expression of LDL-R and HMG-CoAR and decreased the mRNA and protein expression of ACAT2 in Bel-7402 cells. Hyperinand chrysophanol also markedly increased the mRNA expression of CYP7A1. Stimulation with stilbene glycosidesignificantly increased the surface expression of LDL-R and the binding and internalization of LDL. In conclusion, JZN and its four components have close relationship with the process of cholesterol metabolism, emphasizing their promising application as new drug candidates in the treatment of hyperlipidemia.

  18. High density lipoprotein 3 inhibits oxidized low density lipoprotein-induced apoptosis via promoting cholesterol efflux in RAW264.7 cells

    Institute of Scientific and Technical Information of China (English)

    Pei JIANG; Peng-ke YAN; Jian-xiong CHEN; Bing-yang ZHU; Xiao-yong LEI; Wei-dong YIN; Duan-fang LIAO

    2006-01-01

    Aim: To investigate the protective effect of high density lipoprotein 3 (HDL3) on oxidized low density lipoprotein (ox-LDL)-induced apoptosis in RAW264.7 cells.Methods: RAW264.7 cells were exposed to 50 mg/L ox-LDL for various durations up to 48 h, and apoptosis was detected using Hoechst 33258 staining and flow cytometric analysis. Total cholesterol levels were detected by high performance liquid chromatography, cholesterol efflux was determined by Tritium labeling, and the cellular lipid droplets were assayed by oil red O staining. Results: Treatment with 50 mg/L ox-LDL for 12, 24, and 48 h increased the apoptotic rate of RAW264.7 cells in a time-dependent manner. The peak apoptotic rate (47.7%) was observed after 48 h incubation. HDL3 at various concentrations (50 mg/L, 100 mg/L, and 200mg/L) inhibited the ox-LDL (50 mg/L for 48 h)-mediated apoptosis that was accompanied by an increased rate of intracellular cholesterol efflux, and decreased total cholesterol levels in cells in a concentration-dependent manner. Blockage of cholesterol efflux by brefeldin decreased the protective effect of HDL3 on ox-LDL-induced apoptosis. Increase of the cholesterol efflux effected by another cholesterol acceptor, β-cyclodextrin, led to a dramatic decrease in the apoptotic rate of cells. Conclusion: HDL3 antagonizes ox-LDL-induced apoptosis in RAW264.7cells, through reducing the accumulation of toxic cholesterol.

  19. Serum albumin acts as a shuttle to enhance cholesterol efflux from cells.

    Science.gov (United States)

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Phillips, Michael C; Kellner-Weibel, Ginny; Rothblat, George H

    2013-03-01

    An important mechanism contributing to cell cholesterol efflux is aqueous transfer in which cholesterol diffuses from cells into the aqueous phase and becomes incorporated into an acceptor particle. Some compounds can enhance diffusion by acting as shuttles transferring cholesterol to cholesterol acceptors, which act as cholesterol sinks. We have examined whether particles in serum can enhance cholesterol efflux by acting as shuttles. This task was accomplished by incubating radiolabeled J774 cells with increasing concentrations of lipoprotein-depleted sera (LPDS) or components present in serum as shuttles and a constant amount of LDL, small unilamellar vesicles, or red blood cells (RBC) as sinks. Synergistic efflux was measured as the difference in fractional efflux in excess of that predicted by the addition of the individual efflux values of sink and shuttle alone. Synergistic efflux was obtained when LPDS was incubated with cells and LDL. When different components of LPDS were used as shuttles, albumin produced synergistic efflux, while apoA-I did not. A synergistic effect was also obtained when RBC was used as the sink and albumin as shuttle. The previously observed negative association of albumin with coronary artery disease might be linked to reduced cholesterol shuttling that would occur when serum albumin levels are low.

  20. Cholesterol changes in coronary patients after a short behavior modification program.

    Science.gov (United States)

    Sebregts, Ellen H; Falger, Paul R; Bär, Frits W; Kester, Arnold D; Appels, Ad

    2003-01-01

    Serum cholesterol changes after an 8-week behavior modification program for patients with coronary artery disease (CAD) were studied in a randomized controlled clinical trial. Acute myocardial infarction (AMI) or coronary artery bypass grafting (CABG) patients were randomly assigned to the intervention (N = 94) or to usual care (N = 90). After 9 months' follow-up the intervention was effective in reducing total cholesterol and LDL cholesterol levels, particularly in patients with high baseline lipid levels. After correcting for changes in dose of statins during follow-up, effects were weakened, but for patients with high baseline cholesterol levels favorable effects remained. In these patients, the intervention group showed a decline of total cholesterol and LDL cholesterol levels of 20% and 29%, respectively, compared to a 12% and 19% reduction in the control group (p <.01). These effects could not be explained by changes in dietary fat consumption. An unexpected finding was a lower increase in HDL cholesterol in the intervention group than in the control group.

  1. Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China

    Directory of Open Access Journals (Sweden)

    Qing-Jie Chen

    2016-02-01

    Full Text Available Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD. Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged ≥35 years were selected from the Cardiovascular Risk Survey (CRS study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL-C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL-C ratio. Our study also demonstrated that the discriminatory power of the LDL-C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or ≥two of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang.

  2. Appropriate LDL-C-to-HDL-C Ratio Cutoffs for Categorization of Cardiovascular Disease Risk Factors among Uygur Adults in Xinjiang, China.

    Science.gov (United States)

    Chen, Qing-Jie; Lai, Hong-Mei; Chen, Bang-Dang; Li, Xiao-Mei; Zhai, Hui; He, Chun-Hui; Pan, Shuo; Luo, Jun-Yi; Gao, Jing; Liu, Fen; Ma, Yi-Tong; Yang, Yi-Ning

    2016-02-19

    Elevated LDL-C/HDL-C ratio has been shown to be a marker of lipid metabolism as well as a good predictor of coronary artery disease (CAD). Thus, the aim of this study was to investigate whether the LDL-C/HDL-C ratio is useful for detecting cardiovascular disease (CVD) risk factors in general healthy Uygur adults in Xinjiang. A total of 4047 Uygur subjects aged ≥35 years were selected from the Cardiovascular Risk Survey (CRS) study which was carried out from October 2007 to March 2010. Anthropometric data, blood pressure, lipid profile and fasting glucose were measured in all participants. The prevalence, sensitivity, specificity and distance on the receiver operating characteristic (ROC) curve of each LDL-C/HDL-C ratio were calculated. The prevalence of high LDL-C and low HDL-C cholesterol was high and positively correlated with higher LDL-C/HDL-C ratio in the Uygur population. In both men and women, we detected a slight apparent trend of high prevalence of hypertension and hypercholesterolemia with higher LDL-C/HDL-C ratio. Our study also demonstrated that the discriminatory power of the LDL-C/HDL-C ratio for CVD risk factors was slightly stronger in men than in women. Analysis of the shortest distance in the ROC curves for hypertension, dyslipidemia, diabetes, or ≥two of these risk factors suggested a LDL-C/HDL-C ratio cutoff of 2.5 for both men and women. The results of this study showed that a LDL-C/HDL-C ratio cut-off of 2.5 might be used as the predictive marker to detect CVD risk factors among Uygur adults in Xinjiang.

  3. Cholesterol lowering effect of a soy drink enriched with plant sterols in a French population with moderate hypercholesterolemia

    Directory of Open Access Journals (Sweden)

    Bard Jean-Marie

    2008-10-01

    Full Text Available Abstract Background Plant sterols are an established non-pharmacological means to reduce total and LDL blood cholesterol concentrations and are therefore recommended for cholesterol management by worldwide-renown health care institutions. Their efficacy has been proven in many types of foods with the majority of trials conducted in spreads or dairy products. As an alternative to dairy products, soy based foods are common throughout the world. Yet, there is little evidence supporting the efficacy of plant sterols in soy-based foods. The objective of this study was to investigate the effect of a soy drink enriched with plant sterols on blood lipid profiles in moderately hypercholesterolemic subjects. Methods In a randomized, placebo-controlled double-blind mono-centric study, 50 subjects were assigned to 200 ml of soy drink either enriched with 2.6 g plant sterol esters (1.6 g/d free plant sterol equivalents or without plant sterols (control for 8 weeks. Subjects were instructed to maintain stable diet pattern and physical activity. Plasma concentrations of lipids were measured at initial visit, after 4 weeks and after 8 weeks. The primary measurement was the change in LDL cholesterol (LDL-C. Secondary measurements were changes in total cholesterol (TC, non-HDL cholesterol (non-HDL-C, HDL cholesterol (HDL-C and triglycerides. Results Regular consumption of the soy drink enriched with plant sterols for 8 weeks significantly reduced LDL- C by 0.29 mmol/l or 7% compared to baseline (p 96%, and products were well tolerated. Conclusion Daily consumption of a plant sterol-enriched soy drink significantly decreased total, non-HDL and LDL cholesterol and is therefore an interesting and convenient aid in managing mild to moderate hypercholesterolemia.

  4. Effects of Porphyromonas gingivalis lipopolysaccharide on the expression of key genes involved in cholesterol metabolism in macrophages

    Science.gov (United States)

    Liu, Fen; Wang, Yi; Xu, Jing; Liu, Fangqiang

    2016-01-01

    Introduction Cardiovascular diseases are positively correlated with periodontal disease. However, the molecular mechanisms linking atherosclerosis and periodontal infection are not clear. This study aimed to determine whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) altered the expression of genes regulating cholesterol metabolism in macrophages in the presence of low-density lipoprotein (LDL). Material and methods THP-1-derived macrophages were exposed to different concentrations (0.1, 1, 10 µg/ml) of LPS in the presence of 50 µg/ml native LDL. Macrophages were also incubated with 1 µg/ml LPS for varying times (0, 24, 48, or 72 h) in the presence of native LDL. Foam cell formation was determined by oil red O staining and cholesterol content quantification. CD36, lectin-like oxidized LDL receptor-1 (LOX-1), ATP-binding cassette G1 (ABCG1), and acetyl CoA acyltransferase 1 (ACAT1) expression levels were measured by western blot and qRT-PCR. Results Foam cell formation was induced in a time- and concentration-dependent manner as assessed by both morphological and biochemical criteria. Pg-LPS caused downregulation of CD36 and ABCG1 but upregulation of ACAT1, while LOX-1 expression was not affected (p = 0.137). Conclusions Pg-LPS appears to be an important link in the development of atherosclerosis by mechanisms targeting cholesterol homeostasis, namely, excess cholesterol ester formation via ACAT1 and reduced cellular cholesterol efflux via ABCG1. PMID:27695485

  5. The combined effects of genetic variation in the SIRT1 gene and dietary intake of n-3 and n-6 polyunsaturated fatty acids on serum LDL-C and HDL-C levels: a population based study

    Directory of Open Access Journals (Sweden)

    Inamori Tomoko

    2013-01-01

    Full Text Available Abstract Background Dyslipidemia due to high total cholesterol, LDL-cholesterol, triglycerides, or low HDL-cholesterol is an important risk factor for coronary heart disease (CHD. Both SIRT1 and PUFAs can influence the expression of genes for nuclear receptors and transcription factors related to lipid metabolism such as LXRα, LXRβ, PPARα, SREBP-1c. Methods A total of 707 Japanese males and 723 females were randomly selected from the participants who visited a medical center for routine medical check-ups. We analyzed the combined effects of the genotype/haplotype of the SIRT1 gene and dietary n-6/n-3 PUFA intake ratio on the determination of serum lipid levels. Results We found that the SIRT1 gene marked with haplotype 2 was associated with decreased serum LDL-cholesterol and increased HDL-cholesterol levels. In addition, the associations between the SIRT1 haplotype 2 and decreased LDL-C and increased HDL-C levels were only observed in the low n-6/n-3 PUFA intake ratio group, but not in the high n-6/n-3 PUFA intake ratio group. Conclusions Our findings indicate that the combination of genetic variation in the SIRT1 gene and dietary n-6 and/or n-3 PUFA intake influence the determination of inter-individual variations of serum levels of LDL-C and HDL-C.

  6. Cholesterol-lowering drugs: science and marketing.

    Science.gov (United States)

    Garattini, Livio; Padula, Anna

    2017-02-01

    Long-term use of statin therapy is essential to obtain clinical benefits, but adherence is often suboptimal and some patients are also reported to fail because of 'statin resistance'. The identification of PCSK9 as a key factor in the LDL clearance pathway has led to the development of new monoclonal antibodies. Here we critically review the economic evaluations published in Europe and focused on statins. We searched the PubMed database to select the studies published from July 2006 to June 2016 and finally selected 19 articles. Overall, the majority of studies were conducted from a third-party payer's viewpoint and recurred to modelling. Most studies were sponsored by industry and funding seemed to play a pivotal role in the study design. Patients resistant to LDL-C level reduction were considered only in a few studies. The place in therapy of the new class of biologic should be considered a kind of 'third line' for cholesterol-lowering, after patients have failed with restricted dietary regimens and then with current drug therapies. Otherwise they could result in hardly sustainable expenses even for developed countries.

  7. JUPITER to Earth: A statin helps people with normal LDL-C and high hs-CRP, but what does it mean?

    OpenAIRE

    2009-01-01

    The JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) (N Engl J Med 2008; 359:2195–2207) compared rosuvastatin (Crestor) 20 mg daily vs placebo in apparently healthy people who had levels of low-density lipoprotein cholesterol (LDL-C) lower than 130 mg/dL but elevated levels (≥ 2 mg/L) of high-sensitivity C-reactive protein (hs-CRP). Rosuvastatin treatment lowered LDL-C levels by 50% and hs-CRP levels by 37%, accompanied by a 44%...

  8. Statin adherence and treatment LDL-cholesterol response in type 2 diabetes patients

    NARCIS (Netherlands)

    De Vries, Dianna; Voorham, Jaco; Hak, Eelko; Denig, Petra

    2014-01-01

    Background: In clinical practice statins are not optimally used and lipid targets are not achieved in at least a third of the patients. This lack of treatment response could be due to undertreatment (low-dose statin) and low adherence to treatment. Objectives: To determine the relationship between s

  9. Cholesterol and Women's Health

    Science.gov (United States)

    ... can I make to reduce my risk of cardiovascular disease? • Is there medication that can help reduce my cholesterol ... It also helps your body make vitamin D and produces the bile that helps you ...

  10. MD-2 binds cholesterol.

    Science.gov (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I

    2016-02-19

    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  11. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  12. High Total Cholesterol in Peripheral Blood Correlates with Poorer Hearing Recovery in Idiopathic Sudden Sensorineural Hearing Loss

    OpenAIRE

    Nicola Quaranta; Valentina Squeo; Moris Sangineto; Giusi Graziano; Carlo Sabbà

    2015-01-01

    Idiopathic sudden sensorineural hearing loss (ISSHL) is a common otologic emergency whose cause is still unclear. The importance of blood lipids in the pathogenesis of ISSHL is widely reported in literature. In fact elevated levels of low density lipoprotein cholesterol (LDL), total cholesterol (TC) and apolipoprotein B (Apo-B) have been proposed as risk factors for this pathology. No correlation has been described between serum lipid parameters and the prognosis of ISSHL. Aim of the present ...

  13. Longitudinal study of circulating oxidized LDL and HDL and fatty liver: the Cardiovascular Risk in Young Finns Study.

    Science.gov (United States)

    Kaikkonen, Jari E; Kresanov, Petri; Ahotupa, Markku; Jula, Antti; Mikkilä, Vera; Viikari, Jorma S A; Juonala, Markus; Hutri-Kähönen, Nina; Kähönen, Mika; Lehtimäki, Terho; Kangas, Antti J; Soininen, Pasi; Ala-Korpela, Mika; Raitakari, Olli T

    2016-01-01

    Oxidative reactions are thought to play a role in the inflammatory condition called fatty liver. It is unclear whether oxidized lipoprotein lipids or proteins are associated with future fatty liver. In the Cardiovascular Risk in Young Finns Study, we determined the circulating levels of LDL and HDL oxidized lipids and studied their associations with fatty liver assessed by ultrasonography. There were 1286 middle-aged subjects with normal liver and 288 subjects with fatty liver. Analysis of oxidized lipids consisted of conjugated dienes in isolated HDL (oxHDLlipids) and LDL (oxLDLlipids). Oxidized LDL was also measured with a method based on antibodies against oxidized apolipoprotein B (oxLDLprot). After adjustment for age, sex, leisure-time physical activity, body mass index, alcohol intake, smoking, serum LDL and HDL cholesterol as well as particle concentrations, participants with elevated oxLDLlipids (odds ratio for 1-SD change in oxLDLlipids = 1.27, p =0.011) had an increased risk for fatty liver. Similarly, a high oxidation score (oxLDLlipids + oxLDLprot) was directly associated with fatty liver (odds ratio=1.34, p = 0.012). The strongest direct association was seen with a high oxLDLlipids/oxHDLlipids ratio (odds ratio=1.49, p = 0.001). These data suggest that oxidized lipoprotein lipids are linked with the risk of fatty liver in middle-aged adults.

  14. β Common Receptor Mediates Erythropoietin-Conferred Protection on OxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

    Directory of Open Access Journals (Sweden)

    Tzong-Shyuan Lee

    2015-01-01

    Full Text Available Erythropoietin (EPO, the key factor for erythropoiesis, also protects macrophage foam cells from lipid accumulation, yet the definitive mechanisms are not fully understood. β common receptor (βCR plays a crucial role in the nonhematopoietic effects of EPO. In the current study, we investigated the role of βCR in EPO-mediated protection in macrophages against oxidized low-density lipoprotein- (oxLDL- induced deregulation of lipid metabolism and inflammation. Here, we show that βCR expression was mainly in foamy macrophages of atherosclerotic aortas from apolipoprotein E-deficient mice. Results of confocal microscopy and immunoprecipitation analyses revealed that βCR was colocalized and interacted with EPO receptor (EPOR in macrophages. Inhibition of βCR activation by neutralizing antibody or small interfering RNA (siRNA abolished the EPO-conferred protection in oxLDL-induced lipid accumulation. Furthermore, EPO-promoted cholesterol efflux and upregulation of ATP-binding cassette (ABC transporters ABCA1 and ABCG1 were prevented by pretreatment with βCR neutralizing antibody or βCR siRNA. Additionally, blockage of βCR abrogated the EPO-conferred anti-inflammatory action on oxLDL-induced production of macrophage inflammatory protein-2. Collectively, our findings suggest that βCR may play an important role in the beneficial effects of EPO against oxLDL-elicited dysfunction of macrophage foam cells.

  15. The roles of serum ox-LDL/β2-GPI complex in patients with type 2 diabetes mellitus complicated with coronary heart disease%血清ox-LDL/β2-GPI复合物在2型糖尿病合并冠心病中的作用研究

    Institute of Scientific and Technical Information of China (English)

    王良平

    2012-01-01

    目的 探讨血清氧化低密度脂蛋白(ox-LDL)/β2-糖蛋白Ⅰ(β2-GPI)复合物水平与2型糖尿病(T2DM)合并冠心病(CHD)的关系及其临床意义.方法 选取T2DM合并CHD患者68例、单纯T2DM患者69例、单纯CHD患者65例、门诊健康体检者60名.用酶联免疫吸附试验(ELISA)检测血清ox-LDL/β2-GPI复合物水平,并测定空腹血糖(FBG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1C)和空腹血清胰岛素(FINS)、计算体重指数(BMI)及腰臀比(WHR),并作相关分析.结果 T2DM合并CHD组血清ox-LDL/β2-GPI复合物水平均显著高于单纯T2DM组、单纯CHD组和对照组,差异有统计学意义(P<0.05);T2DM合并CHD组ox-LDL/β2-GPI复合物水平均与TG和HOMA-IR呈正相关(r=0.219、0.228,P均<0.01);TG和ox-LDL/β2-GPI复合物是T2DM危险因素,ox-LDL/β2-GPI复合物和HbA1C是T2DM合并CHD的危险因素.结论 血清ox-LDL/β2-GPI复合物与T2DM合并CHD的发病有一定联系.%Objective To investigate the roles of serum oxidized low density lipoprotein ( ox-LDL)/beta,-glycoprotein I ( β2-GPI) complex in type 2 diabetes mellitus ( T2DM )patients complicated with coronary heart disease ( CHD )and its clinical significance. Methods Serum samples were collected from 68 T2DM patients complicated with CHD,69 patients with T2DM,65 patients with CHD and 60 healthy controls. Serum ox-LDL/β2-GPI complex were measured by enzyme-linked immunosorbent assay( ELISA ), and the fasting blood glucose( FBG ), total cholesterol( TC ), triglyceride( TG ), high-density lipoprotein cholesterol ( HDL-C ), low-density lipoprotein cholesterol ( LDL-C ), glycosylated hemoglobin ( HbA1c ),fasting serum insulin( FINS ),body mass index ( BMI )and waist to hip ratio( WHR ) were determined and analyzed. Results The T2DM patients complicated with CHD had significantly higher levels of ox-LDL/β2-GPI complex than T2DM group,CHD group and

  16. Serum Cholesterol Reduction Efficacy of Biscuits with Added Plant Stanol Ester

    Directory of Open Access Journals (Sweden)

    Wantanee Kriengsinyos

    2015-01-01

    Full Text Available This study’s aim was to test the low-density lipoprotein cholesterol- (LDL-c- lowering efficacy of biscuits containing 2 g of plant stanols, which corresponded to 3.4 g of plant stanol esters. The biscuit is a new food format that can be consumed as a snack. In a double-blind, placebo-controlled parallel design study, 119 mildly to moderately hypercholesterolemic volunteers were randomized to plant stanol or control groups. Subjects were comparable in age, gender, lipid profiles, and body mass index. They consumed a control biscuit once a day for a two-week period, followed by a four-week intervention period that either had a plant stanol ester biscuit or a control. During the habitual diet, one biscuit per day was consumed at any time that subjects wished. Serum lipid profiles were measured at the first day of run-in, at baseline, and at the study’s end. Compared to the control, the total cholesterol (TC, LDL-c, and the LDL-to-high-density lipoprotein (LDL/HDL ratio had serum reductions of 4.9%, 6.1%, and 4.3%, respectively, and were observed after 4 weeks of biscuit consumption with added plant stanols (P < 0.05. A significantly higher reduction in LDL-c (8.9% and LDL/HDL ratio (11.4% was measured in those taking a plant stanol biscuit with a meal compared to those who consumed a plant stanol biscuit without other food. In conclusion, incorporating plant stanols into a biscuit is an attractive, convenient, and acceptable way to modestly lower elevated cholesterol concentrations. For optimal efficacy, biscuits should be consumed with a meal as part of a healthy diet.

  17. NF-kB activity-dependent P-selectin involved in ox-LDL-induced foam cell formation in U937 cell

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yi, E-mail: wangyi2004a@126.com [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China); Wang, Xiang; Sun, Minghui; Zhang, Zhenyu; Cao, Heng; Chen, Xiaoqing [Department of Cardiology, Shanghai First People' s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200080 (China)

    2011-08-05

    Highlights: {yields} Ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. {yields} Ox-LDL induced expression of P-selectin through degradation of IkBa and augment of NF-kB activity and protein level during macrophage-derived foam cell formation. {yields} P-selectin and NF-kB may be identified as pivotal regulators of ox-LDL-induced foam cell formation. {yields} Therapy based on the inhibition of P-selectin and NF-kB may complement conventional treatments to prevent atherosclerosis. -- Abstract: Oxidized low-density lipoprotein (ox-LDL) plays a critical role in regulation of atherosclerosis. However, little is known about the role of Nuclear factor kB (NF-kB) activity-dependent P-selectin in ox-LDL-induced foam cell formation during atherosclerosis. In this study, we first investigated ox-LDL induced foam cell formation in the human U937 promonocytic cell line in a dose- and time-dependent manner. Treatment of U937 cells with ox-LDL increased lipid accumulation as well as intracellular cholesterol content. Next, a comparative analysis of gene expression profiling using cDNA microarray and Real-time-PCR indicated that ox-LDL exposure induced, in three treated groups, an extremely marked increase in the mRNA level of P-selectin. Protein levels of P-selectin and its upstream regulators IkBa and NF-kB showed that NF-kB pathway is involved in the ox-LDL-induced foam cell formation. Finally, overexpression of NF-kB significantly accelerated, whereas, inhibition of NF-kB with siRNA remarkably attenuated ox-LDL-induced macrophage-derived foam cell formation. It was concluded that the activity of NF-kB is augmented during macrophage-derived foam cell formation. Activation of NF-kB increased, whereas, inhibition of NF-kB decreased ox-LDL-induced P-selectin expression and lipid accumulation in macrophages, suggesting ox-LDL induced expression of P-selectin through degradation of IkBa and activation of NF-kB in the

  18. [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.

  19. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Xiaolin [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Li, Qian [Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai (China); Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China); Wang, Yiqing, E-mail: yiqingwangbiopaper@163.com [Department of Cardiothoracic Surgery, Huashan Hospital, Fudan University, Shanghai 200032 (China)

    2013-11-15

    Highlights: •Arctigenin enhanced cholesterol efflux in oxLDL-loaded THP-1 macrophages. •The expression of ABCA1, ABCG1 and apoE was upregulated in arctigenin-treated cells. •Arctigenin promoted the expression of PPAR-γ and LXR-α. •Inhibition of PPAR-γ or LXR-α reversed arctigenin-mediated biological effects. •Arctigenin promotes cholesterol efflux via activation of PPAR-γ/LXR-α/ABCA1 pathway. -- Abstract: Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

  20. HDL functionality in reverse cholesterol transport--Challenges in translating data emerging from mouse models to human disease.

    Science.gov (United States)

    Lee-Rueckert, Miriam; Escola-Gil, Joan Carles; Kovanen, Petri T

    2016-07-01

    Whereas LDL-derived cholesterol accumulates in atherosclerotic lesions, HDL particles are thought to facilitate removal of cholesterol from the lesions back to the liver thereby promoting its fecal excretion from the body. Because generation of cholesterol-loaded macrophages is inherent to atherogenesis, studies on the mechanisms stimulating the release of cholesterol from these cells and its ultimate excretion into feces are crucial to learn how to prevent lesion development or even induce lesion regression. Modulation of this key anti-atherogenic pathway, known as the macrophage-specific reverse cholesterol transport, has been extensively studied in several mouse models with the ultimate aim of applying the emerging knowledge to humans. The present review provides a detailed comparison and critical analysis of the various steps of reverse cholesterol transport in mouse and man. We attempt to translate this in vivo complex scenario into practical concepts, which could serve as valuable tools when developing novel HDL-targeted therapies.

  1. Effects of apple cider vinegars produced with different techniques on blood lipids in high-cholesterol-fed rats.

    Science.gov (United States)

    Budak, Nilgun H; Kumbul Doguc, Duygu; Savas, Cagri M; Seydim, Atif C; Kok Tas, Tugba; Ciris, Metin I; Guzel-Seydim, Zeynep B

    2011-06-22

    Red delicious apples were used to produce natural apple cider with and without inclusion of maceration. Traditional surface and industrial submersion methods were then applied to make vinegar from apple ciders. Apple cider vinegar samples produced with inclusion of maceration in the surface method had the highest total phenolic content, chlorogenic acid, ORAC, and TEAC levels. Cholesterol and apple vinegar samples were administered using oral gavage to all groups of rats except the control group. Apple cider vinegars, regardless of the production method, decreased triglyceride and VLDL levels in all groups when compared to animals on high-cholesterol diets without vinegar supplementation. Apple cider vinegars increased total cholesterol and HDL and LDL cholesterol levels and decreased liver function tests when compared to animals on a high-cholesterol diet without vinegar supplementation. A high-cholesterol diet resulted in hepatic steatosis. VSBM and VSB groups significantly decreased steatosis.

  2. 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

    Anthocyanin-rich beverages have shown beneficial effects on coronary heart disease in epidemiological and intervention studies. In the present study, we investigated the effect of black currant anthocyanins on atherosclerosis. Watanabe Heritable Hyperlipidemic rabbits (n = 61) were fed either...... 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...

  3. Lower low density lipid cholesterol levels are associated with Parkinson’s disease

    OpenAIRE

    Huang, Xuemei; Chen, Honglei; Miller, William C.; Mailman, Richard B.; Woodard, Jennifer L.; Chen, Peter C.; Xiang, Dong; Murrow, Richard W.; Wang, Yi-Zhe; Poole, Charles

    2007-01-01

    The apolipoprotein E (APOE) ε2 allele has been associated with both Parkinson’s disease (PD) and lower low density lipoprotein cholesterol (LDL-C). The study is to test the hypothesis that lower LDL-C may be associated with PD. This case-control study used fasting lipid profiles obtained from 124 PD cases and 110 controls, the PD cases recruited from consecutive cases presenting at our tertiary Movement Disorder Clinic, and controls recruited from the spouse populations of the same clinic. Mu...

  4. Associations between oxidized LDL to LDL ratio, HDL and vascular calcification in the feet of hemodialysis patients.

    Science.gov (United States)

    An, Won Suk; Kim, Seong-Eun; Kim, Ki-Hyun; Bae, Hae-Rahn; Rha, Seo-Hee

    2009-01-01

    Cardiovascular mortality is associated with vascular calcification (VC) in hemodialysis (HD) patients. The present study was designed to find factors related with medial artery calcification on the plain radiography of feet by comparing C-reactive protein (CRP), plasminogen activator inhibitor type 1 (PAI-1) and lipid profile including oxidized low density lipoprotein (ox-LDL) and to elucidate associations among these factors in HD patients. Forty-eight HD patients were recruited for this study. VC in the feet was detected in 18 patients (37.5%) among total patients and 12 patients (85.7%) among diabetic patients. Diabetes, cardiovascular disease (CVD), pulse pressure, ox-LDL/LDL were higher and high density lipoprotein (HDL) was lower in patients with VC than in patients without VC. Negative associations were found between HDL and CRP, PAI-1. PAI-1 had positive association with ox-LDL/LDL. History of CVD was the only determinant of vascular calcification on the plain radiography of feet. Ox-LDL/LDL, HDL, CRP, and PAI-1 were closely related with one another in HD patients. History of CVD is the most important factor associated with the presence of VC and low HDL and relatively high oxidized LDL/LDL ratio may affect VC formation on the plain radiography in the feet of HD patients.

  5. On the mechanism of plasma cholesterol reduction in the rat given probucol.

    Science.gov (United States)

    Balasubramaniam, S; Beins, D M; Simons, L A

    1981-11-01

    1. The effects of the cholesterol-lowering drug probucol on lipoprotein metabolism and on the key enzymes that regulate hepatic cholesterol metabolism in the rat were studied. 2. Probucol given for 2 weeks was accompanied by a significant reduction in plasma concentrations of low-density and high-density lipoproteins (LDL,HDL). The fractional catabolic rates of the apolipoproteins of HDL and LDL (apoHDL, apoLDL) were not affected by probucol, although the absolute rates of catabolism of both the apolipoproteins were significantly reduced. 3. The activities of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase and cholesterol 7 alpha-mono-oxygenase, as well as the rate of hepatic sterol synthesis, were unchanged during the first 2 weeks of probucol. More prolonged probucol led to inhibition of the activity of these enzymes and reduction in sterol synthesis, although the liver cellular content of cholesterol significantly increased. 4. It is postulated that a principal mode of action of the drug is to reduce the rate of lipoprotein synthesis.

  6. Ability of Lactobacillus plantarum JR64 isolated from noni juice in lowering Cholesterol in vivo

    Directory of Open Access Journals (Sweden)

    Lanjar Sumarno

    2011-07-01

    Full Text Available Recently public’s attention to the importance of healthy food increases rapidly. Probiotic based food exploiting lactic acid bacteria is among the healthy food. Lactobacillus plantarum JR64 isolate from Morinda citrifolia fruit was assessed for its probiotic in-vivo by using Wistar  Rat. The purpose of this research was to study the ability of probiotic Lactobacillus plantarum JR64 in lowering serum LDL (Low Density Lipoprotein of Wistar Rat. Twenty Rats were grouped into 4, each group consisted of 5 Rats. First Group was a negative control  given standard normal diet of 20 gr/day plus aquadest. Second Grup was a positive control given cholesterol normal diet 20 gr /day plus Propil Tio Urasil (PTU 60 mg/kg body weight/day. Third Group was supplemented with normal diet 20 gr /day plus Propil Tio Urasil (PTU 60 mg  kg body weight /day and  1012 CFU Lactobacillus plantarum JR64. Fourth Group was the same as third Group unless the probiotic using commercial probiotic Lactobacillus bulgariccus at 1012 CFU. Blood samples were withdrawn for measurement of total cholesterol, triglyceride, High Density Lipoprotein (HDL, and Low Density Lipoprotein (LDL cholesterol every week and measured by using spectrophotometer with 546 nanometers wavelength. The results show that probiotic Lactobacillus plantarum JR64 isolated from noni juice significantly (p < 0,01 reduce Low Density Lipoprotein (LDL and Triglyceride in vivo  and tend to reduce High Density Lipoprotein (HDL and total cholesterol.

  7. Low high-density lipoprotein cholesterol is a residual risk factor associated with long-term clinical outcomes in diabetic patients with stable coronary artery disease who achieve optimal control of low-density lipoprotein cholesterol.

    Science.gov (United States)

    Ogita, Manabu; Miyauchi, Katsumi; Miyazaki, Tadashi; Naito, Ryo; Konishi, Hirokazu; Tsuboi, Shuta; Dohi, Tomotaka; Kasai, Takatoshi; Yokoyama, Takayuki; Okazaki, Shinya; Kurata, Takeshi; Daida, Hiroyuki

    2014-01-01

    Diabetes mellitus is recognized an independent risk factor for coronary artery disease (CAD) and mortality. Clinical trials have shown that statins significantly reduce cardiovascular events in diabetic patients. However, residual cardiovascular risk persists despite the achievement of target low-density lipoprotein cholesterol (LDL-C) levels with statin. High-density lipoprotein cholesterol (HDL-C) is an established coronary risk factor that is independent of LDL-C levels. We evaluated the impact of HDL-C on long-term mortality in diabetic patients with stable CAD who achieved optimal LDL-C. We enrolled 438 consecutive diabetic patients who were scheduled for percutaneous coronary intervention between 2004 and 2007 at our institution. We identified 165 patients who achieved target LDL-C diabetic patients with low-HDL-C who achieved optimal LDL-C (6.9 vs 17.9 %, log-rank P = 0.030). Multivariate Cox regression analysis showed that HDL-C is significantly associated with clinical outcomes (adjusted hazard ratio for MACE 1.33, 95 % confidence interval 1.01-1.75, P = 0.042). Low HDL-C is a residual risk factor that is significantly associated with long-term clinical outcomes among diabetic patients with stable CAD who achieve optimal LDL-C levels.

  8. Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia.

    Science.gov (United States)

    Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

    2015-12-17

    Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

  9. Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Li-Chen Lee

    2015-12-01

    Full Text Available Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD. Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8, standard diet (control; and experimental (n = 32, HCD. The 32 hamsters were further divided into four groups (n = 8 per group to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC, triacylglycerol (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C, LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia.

  10. Hypolipidemic Effect of Tomato Juice in Hamsters in High Cholesterol Diet-Induced Hyperlipidemia

    Science.gov (United States)

    Lee, Li-Chen; Wei, Li; Huang, Wen-Ching; Hsu, Yi-Ju; Chen, Yi-Ming; Huang, Chi-Chang

    2015-01-01

    Tomato is a globally famous food and contains several phytonutrients including lycopene, β-carotene, anthocyanin, and flavonoids. The increased temperature used to produce tomato juice, ketchup, tomato paste and canned tomato enhances the bioactive composition. We aimed to verify the beneficial effects of processed tomato juice from Kagome Ltd. (KOT) on hypolipidemic action in hamsters with hyperlipidemia induced by a 0.2% cholesterol and 10% lard diet (i.e., high-cholesterol diet (HCD)). Male Golden Syrian hamsters were randomly divided into two groups for treatment: normal (n = 8), standard diet (control); and experimental (n = 32), HCD. The 32 hamsters were further divided into four groups (n = 8 per group) to receive vehicle or KOT by oral gavage at 2787, 5573, or 13,934 mg/kg/day for six weeks, designated the HCD-1X, -2X and -5X groups, respectively. The efficacy and safety of KOT supplementation was evaluated by lipid profiles of serum, liver and feces and by clinical biochemistry and histopathology. HCD significantly increased serum levels of total cholesterol (TC), triacylglycerol (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), LDL-C/HDL-C ratio, hepatic and fetal TC and TG levels, and degree of fatty liver as compared with controls. KOT supplementation dose-dependently decreased serum TC, TG, LDL-C levels, LDL-C/HDL-C ratio, hepatic TC and TG levels, and fecal TG level. Our study provides experiment-based evidence to support that KOT may be useful in treating or preventing the onset of hyperlipidemia. PMID:26694461

  11. Traditional dietary pattern is associated with elevated cholesterol among the Inuit of Nunavik.

    Science.gov (United States)

    Labonté, Marie-Ève; Dewailly, Eric; Lucas, Michel; Chateau-Degat, Marie-Ludivine; Couture, Patrick; Lamarche, Benoît

    2014-08-01

    Our cross-sectional study assessed the associations between dietary patterns and cardiovascular disease (CVD) risk factors among Nunavik Inuit. This study was conducted as part of the 2004 Nunavik Inuit Health Survey, which included the collection of clinical measurements, plasma samples, and diet information from a food frequency questionnaire. A sample of 666 Inuit aged 18 years and older was included in our analyses. Dietary patterns were generated by principal component analysis. Multivariate general linear models adjusting for sex, age, waist circumference, and other potential confounders were used to examine associations between dietary patterns and CVD risk factors. Four distinct patterns were identified, namely the traditional, Western, nutrient-poor food, and healthy patterns. The traditional pattern showed positive associations with plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein B100, LDL peak particle diameter, and oxidized LDL (all P values for trend≤0.04), but showed no association with the total cholesterol:high-density lipoprotein cholesterol ratio or with inflammatory biomarkers (all P values for trend ≥0.19). The nutrient-poor food pattern was positively associated with oxidized LDL (P=0.04), but inversely associated with high-sensitivity C-reactive protein (Ppatterns showed no association with any CVD risk factor. Our data show that high adherence to a traditional pattern among Nunavik Inuit is not associated with important changes in CVD risk factors, with the exception of a slight elevation in cholesterol concentrations, most likely attributable to increased n-3 fatty acid intake. Dietary patterns reflecting the recent introduction of market foods in the Inuit diet appear to exert a trivial influence on CVD risk factors.

  12. Cholesterol and prostate cancer.

    Science.gov (United States)

    Pelton, Kristine; Freeman, Michael R; Solomon, Keith R

    2012-12-01

    Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models, which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations.

  13. Effect of Lactobacillus acidophilus NS1 on plasma cholesterol levels in diet-induced obese mice.

    Science.gov (United States)

    Song, M; Park, S; Lee, H; Min, B; Jung, S; Park, S; Kim, E; Oh, S

    2015-03-01

    We investigated the probiotic properties of Lactobacillus acidophilus NS1, such as acid resistance, bile tolerance, adherence to HT-29 cells, and cholesterol assimilation activity. In an animal study, 7-wk-old male C57BL/6 mice were fed a normal diet, a high-fat diet (HFD), or an HFD with L. acidophilus NS1 (ca. 1.0×10(8) cfu/mL) for 10 wk. Total cholesterol and low-density lipoprotein (LDL) cholesterol levels were significantly lower in mice fed an HFD with L. acidophilus NS1 than in those fed an HFD only, whereas high-density lipoprotein cholesterol levels were similar between these 2 groups. To understand the mechanism of the cholesterol-lowering effect of L. acidophilus NS1 on the HFD-mediated increase in plasma cholesterol levels, we determined mRNA levels of genes involved in cholesterol homeostasis in the liver. Expression of sterol regulatory element-binding protein 2 (Srebp2) and LDL receptor (Ldlr) in the liver was dramatically reduced in mice fed a HFD compared with those fed a normal diet. When L. acidophilus NS1 was administered orally to HFD-fed mice, an HFD-induced suppression of Srebp2 and Ldlr expression in the liver was abolished. These results suggest that the oral administration of L. acidophilus NS1 to mice fed an HFD increased the expression of Srebp2 and Ldlr in the liver, which was inhibited by high fat intake, thus leading to a decrease in plasma cholesterol levels. Lactobacillus acidophilus NS1 could be a useful probiotic microorganism for cholesterol-lowering dairy products and the improvement of hyperlipidemia and hepatic lipid metabolism.

  14. Regulation of plasma LDL: the apoB paradigm.

    NARCIS (Netherlands)

    Sniderman, A.D.; Graaf, J. de; Couture, P.; Williams, K.; Kiss, R.S.; Watts, G.F.

    2010-01-01

    The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholestero

  15. Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol-glucuronides

    Science.gov (United States)

    Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major...

  16. Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Lotta, Luca A; Sharp, Stephen J; Burgess, Stephen;

    2016-01-01

    Importance: Low-density lipoprotein cholesterol (LDL-C)-lowering alleles in or near NPC1L1 or HMGCR, encoding the respective molecular targets of ezetimibe and statins, have previously been used as proxies to study the efficacy of these lipid-lowering drugs. Alleles near HMGCR are associated with...

  17. Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction.

    Science.gov (United States)

    Henry, Courtney A; Lyon, Ronald A; Ling, Hua

    2016-01-01

    Multiple categories of medications have been developed to manage lipid profiles and reduce the risk of cardiovascular events in patients with heart disease. However, currently marketed medications have not solved the problems associated with preventing and treating cardiovascular diseases completely. A substantial population of patients cannot take advantage of statin therapy due to statin intolerance, heart failure, or kidney hemodialysis, suggesting a need for additional effective agents to reduce low-density lipoprotein cholesterol (LDL-C) levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) was discovered in 2003 and subsequently emerged as a novel target for LDL-C-lowering therapy. Evolocumab is a fully human monoclonal immunoglobulin G2 (IgG2) directed against human PCSK9. By inactivating PCSK9, evolocumab upregulates LDL receptors causing increased catabolism of LDL-C and the consequent reduction of LDL-C levels in blood. Overall, evolocumab has had notable efficacy, with LDL-C reduction ranging from 53% to 75% in monotherapy and combination therapies, and is associated with minor adverse effects. However, studies regarding the ability of evolocumab to reduce mortality as well as long-term safety concerns are limited. The fact that the drug was introduced at a cost much higher than the existing medications and shows a low incremental mortality benefit suggests that many payers will consider evolocumab to have an unfavorable cost-benefit ratio.

  18. How Do PCSK9 Inhibitors Stack Up to Statins for Low-Density Lipoprotein Cholesterol Control?

    Science.gov (United States)

    Zimmerman, Marj P.

    2015-01-01

    Despite advances in the approach toward treating hypercholesterolemia and widespread access to statin medications, not all people are able to reach target low-density lipoprotein cholesterol (LDL-C) levels to reduce their cardiovascular risk. Some of the reasons include the inability to tolerate statin therapy, LDL-C levels that remain high even in the presence of statin therapy, and a familial disorder that is characterized by extremely high levels of LDL-C. A new therapeutic class, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, represents a novel and promising approach to reducing LDL-C levels using a mechanism at the LDL receptor level. The recent approval of the first 2 PCSK9 inhibitors and the anticipated approval of the third agent in this class within approximately 1 year may provide clinicians powerful new weapons to lower LDL-C levels in patients who are not satisfactorily managed with statins. However, the results of long-term studies of the ability of these new medications to influence cardiovascular outcomes will not be known for several years. PMID:26702335

  19. Identification of miR-148a as a novel regulator of cholesterol metabolism

    Science.gov (United States)

    Goedeke, Leigh; Rotllan, Noemi; Canfrán-Duque, Alberto; Aranda, Juan F.; Ramírez, Cristina M.; Araldi, Elisa; Lin, Chin-Sheng; Anderson, Norma N.; Wagschal, Alexandre; de Cabo, Rafael; Horton, Jay D.; Lasunción, Miguel A.; Näär, Anders M.; Suárez, Yajaira; Fernández-Hernando, Carlos

    2015-01-01

    The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL-cholesterol (LDL-C). While the transcriptional regulation of LDLR is well-characterized, the post-transcriptional mechanisms which govern LDLR expression are just beginning to emerge. Here, we developed a high-throughput genome-wide screening assay to systematically identify microRNAs (miRNAs) that regulate LDLR activity in human hepatic cells. From this screen, we characterize miR-148a as a negative regulator of LDLR expression and activity, and define a novel SREBP1-mediated pathway by which miR-148a regulates LDL-C uptake. Importantly, inhibition of miR-148a increases hepatic LDLR expression and decreases plasma LDL-C in vivo. We also provide evidence that miR-148a regulates hepatic ABCA1 expression and circulating HDL-C levels. Collectively, these studies uncover miR-148a as an important regulator of hepatic LDL-C clearance through direct regulation of LDLR expression, and demonstrate the therapeutic potential of inhibiting miR-148a to ameliorate the elevated LDL-C/HDL-C ratio, a prominent risk factor for cardiovascular disease. PMID:26437365

  20. Enrichment of LDL with EPA and DHA decreased oxidized LDL-induced apoptosis in U937 cells.

    Science.gov (United States)

    Wu, Tianying; Geigerman, Cissy; Lee, Ye-Sun; Wander, Rosemary C

    2002-08-01

    Oxidized LDL (oxLDL) may contribute to the accumulation of apoptotic cells in atherosclerotic plaques. Although it is well established in monophasic chemical systems that the highly unsaturated EPA and DHA will oxidize more readily than FA that contain fewer double bonds, our previous studies showed that enrichment of LDL, which has discrete polar and nonpolar phases, with these FA did not increase oxidation. The objective of this study was to compare the extent of apoptosis induced by EPA/DHA-rich oxLDL to that induced by EPA/DHA-non-rich oxLDL in U937 cells. LDL was obtained from one healthy subject three times before and after supplementation for 5 wk with 15 g/d of fish oil (FO), an amount easily obtainable from a diet that contains fatty fish. After supplementation, an EPA/DHA-rich LDL was obtained. Oxidative susceptibility of LDL, as determined by measuring the formation of conjugated dienes and the accumulation of cholesteryl ester hydroperoxides, was not higher in EPA/DHA-rich LDL. The oxLDL-induced cell apoptosis was detected by the activation of caspase-3, the translocation of PS to the outer surface of the plasma membrane using the Annexin V-fluorescein isothiocyanate binding assay, and the presence of chromatin condensation and nuclear fragmentation using the 4,6-diamidino-2-phenylindole staining assay. All three measures showed that after FO supplementation, EPA/DHA-rich oxLDL-induced cell apoptosis decreased. The decrease was not related to the concentration of lipid hydroperoxides. This study suggests that a possible protective effect of EPA/DHA-rich diets on atherosclerosis may be through lessening cell apoptosis in the arterial wall.

  1. Orbitofrontal cholesterol granuloma.

    Science.gov (United States)

    Chow, L P; McNab, A A

    2005-02-01

    Cholesterol granuloma of the orbital bones is a rare but readily recognisable condition. It is an osteolytic lesion with a granulomatous reaction surrounding cholesterol crystals, old haemorrhage and a fibrous capsule. There is a male preponderance and it usually occurs in young or middle-aged men. It is treatable with drainage and curettage via an orbitotomy, and craniotomy or wide bone removal is almost never required. Six cases of this condition were reviewed to highlight the typical clinical presentation, computed tomography and magnetic resonance results, and surgical management.

  2. Cholesterol and myelin biogenesis.

    Science.gov (United States)

    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  3. Augmented atherogenesis in LDL receptor deficient mice lacking both macrophage ABCA1 and ApoE.

    Directory of Open Access Journals (Sweden)

    Bart Lammers

    Full Text Available AIM: ABCA1 protects against atherosclerosis by facilitating cholesterol efflux from macrophage foam cells in the arterial wall to extracellular apolipoprotein (apo A-I. In contrast to apoA-I, apoE is secreted by macrophages and can, like apoA-I, induce ABCA1-mediated cholesterol efflux. Yet, the combined effect of macrophage ABCA1 and apoE on lesion development is unexplored. METHODS AND RESULTS: LDL receptor knockout (KO mice were transplanted with bone marrow from ABCA1/apoE double KO (dKO mice, their respective single KO's, and wild-type (WT controls and were challenged with a high-fat/high-cholesterol diet for 9 weeks. In vitro cholesterol efflux experiments showed no differences between ABCA1 KO and dKO macrophages. The serum non-HDL/HDL ratio in dKO transplanted mice was 1.7-fold and 2.4-fold (p<0.01 increased compared to WT and ABCA1 KO transplanted mice, respectively. The atherosclerotic lesion area in dKO transplanted animals (650±94×10(3 µm(2, however, was 1.9-fold (p<0.01 and 1.6-fold (p<0.01 increased compared to single knockouts (ABCA1 KO: 341±20×10(3 µm(2; apoE KO: 402±78×10(3 µm(2, respectively and 3.1-fold increased (p<0.001 compared to WT (211±20×10(3 µm(2. When normalized for serum cholesterol exposure, macrophage ABCA1 and apoE independently protected against atherosclerotic lesion development (p<0.001. Moreover, hepatic expression levels of TNFα and IL-6 were highly induced in dKO transplanted animals (3.0-fold; p<0.05, and 4.3-fold; p<0.001, respectively. In agreement, serum IL-6 levels were also enhanced in ABCA1 KO transplanted mice (p<0.05 and even further enhanced in dKO transplanted animals (3.1-fold as compared to ABCA1 KO transplanted animals; p<0.05. CONCLUSIONS: Combined deletion of macrophage ABCA1 and apoE results in a defect in cholesterol efflux and, compared to ABCA1 KO transplanted mice, elevated serum total cholesterol levels. Importantly, these mice also suffer from enhanced systemic and hepatic

  4. The dynamin chemical inhibitor dynasore impairs cholesterol trafficking and sterol-sensitive genes transcription in human HeLa cells and macrophages.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Girard

    Full Text Available Intracellular transport of cholesterol contributes to the regulation of cellular cholesterol homeostasis by mechanisms that are yet poorly defined. In this study, we characterized the impact of dynasore, a recently described drug that specifically inhibits the enzymatic activity of dynamin, a GTPase regulating receptor endocytosis and cholesterol trafficking. Dynasore strongly inhibited the uptake of low-density lipoprotein (LDL in HeLa cells, and to a lower extent in human macrophages. In both cell types, dynasore treatment led to the abnormal accumulation of LDL and free cholesterol (FC within the endolysosomal network. The measure of cholesterol esters (CE further showed that the delivery of regulatory cholesterol to the endoplasmic reticulum (ER was deficient. This resulted in the inhibition of the transcriptional control of the three major sterol-sensitive genes, sterol-regulatory element binding protein 2 (SREBP-2, 3-hydroxy-3-methyl-coenzymeA reductase (HMGCoAR, and low-density lipoprotein receptor (LDLR. The sequestration of cholesterol in the endolysosomal compartment impaired both the active and passive cholesterol efflux in HMDM. Our data further illustrate the importance of membrane trafficking in cholesterol homeostasis and validate dynasore as a new pharmacological tool to study the intracellular transport of cholesterol.

  5. Periodontal treatment decreases plasma oxidized LDL level and oxidative stress.

    Science.gov (United States)

    Tamaki, Naofumi; Tomofuji, Takaaki; Ekuni, Daisuke; Yamanaka, Reiko; Morita, Manabu

    2011-12-01

    Periodontitis induces excessive production of reactive oxygen species in periodontal lesions. This may impair circulating pro-oxidant/anti-oxidant balance and induce the oxidation of low-density lipoprotein (LDL) in blood. The purpose of this study was to monitor circulating oxidized LDL and oxidative stress in subjects with chronic periodontitis following non-surgical periodontal treatment. Plasma levels of oxidized LDL and oxidative stress in 22 otherwise healthy non-smokers with chronic periodontitis (mean age 44.0 years) were measured at baseline and at 1 and 2 months after non-surgical periodontal treatment. At baseline, chronic periodontitis patients had higher plasma levels of oxidized LDL and oxidative stress than healthy subjects (p surgical periodontal treatment were effective in decreasing oxLDL, which was positively associated with a reduction in circulating oxidative stress.

  6. [PCSK9 inhibitors: new treatment to lower cholesterol].

    Science.gov (United States)

    Gencer, Baris; Rodondi, Nicolas; Mach, François

    2016-03-01

    The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors appear to represent an important development in the management of hypercholesterolemia. US Food and Drug Administration and European Medicines Agency approved alirocumab and evolocumab, injected drugs administered subcutaneously every 2 or 4 weeks, for patients with hypercholesterolemia, such as those who not reached the cholesterol targets or those with intolerance to statin, especially in secondary prevention or familial hypercholesterolemia. This decision is based on several clinical trials suggesting that these drugs have a powerful effect on levels of LDL-cholesterol with an acceptable safety compared to placebo. Large clinical studies are currently performed to assess the impact of PCSK9 inhibitors on major adverse cardiovascular events in secondary prevention.

  7. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible anti-atherosc

  8. Comparison between the Effects of Intraperitoneal Injection of LDL and Intravenous Injection of LDL on Arterial Endothelial Cells Apoptosis

    Institute of Scientific and Technical Information of China (English)

    王丽; 秦瑾; 刘正湘

    2003-01-01

    Summary: To observe the effect of oxidized low density lipoprotein (OxLDL) on arterial endothelialcells apoptosis in vivo, we established a model in which Sprague-Dawley rats were given intraperi-toneal and intravenous injection of unmodified LDL (8 mg/kg every day) via the tail vein. Sevendays after the injection, the aortic endothelial cells specimens were prepared by an en face preparationof rat aorta. The apoptotic cells were identified and counted by in situ nick and labelling (TUNEL)method and light microcopy. The numbers of the apoptotic cells were 12.52±4.71/field in the in-traperitoneal injection control group, 11.41±2.94/field in the intravenous injection control group,22.98±8. 01/field in the intraperitoneal injection LDL group and 103. 8 ± 11.5/field in the intra-venous injection LDL group, respectively. The difference was significant between injection LDLgroup and control (P<0. 01), and the difference was also significant between two LDL injectiongroups (P<0. 01). These findings suggest that injection of LDL can induce apoptosis in arterial en-dothelial cells and the effect is especially significant with intravenous injection LDL. After injection,oxidative modification of LDL may occur in local arteries and causes injury to the endothelial cells.

  9. Cellular cholesterol delivery, intracellular processing and utilization for biosynthesis of steroid hormones

    Directory of Open Access Journals (Sweden)

    Azhar Salman

    2010-06-01

    Full Text Available Abstract Steroid hormones regulate diverse physiological functions such as reproduction, blood salt balance, maintenance of secondary sexual characteristics, response to stress, neuronal function and various metabolic processes. They are synthesized from cholesterol mainly in the adrenal gland and gonads in response to tissue-specific tropic hormones. These steroidogenic tissues are unique in that they require cholesterol not only for membrane biogenesis, maintenance of membrane fluidity and cell signaling, but also as the starting material for the biosynthesis of steroid hormones. It is not surprising, then, that cells of steroidogenic tissues have evolved with multiple pathways to assure the constant supply of cholesterol needed to maintain optimum steroid synthesis. The cholesterol utilized for steroidogenesis is derived from a combination of sources: 1 de novo synthesis in the endoplasmic reticulum (ER; 2 the mobilization of cholesteryl esters (CEs stored in lipid droplets through cholesteryl ester hydrolase; 3 plasma lipoprotein-derived CEs obtained by either LDL receptor-mediated endocytic and/or SR-BI-mediated selective uptake; and 4 in some cultured cell systems from plasma membrane-associated free cholesterol. Here, we focus on recent insights into the molecules and cellular processes that mediate the uptake of plasma lipoprotein-derived cholesterol, events connected with the intracellular cholesterol processing and the role of crucial proteins that mediate cholesterol transport to mitochondria for its utilization for steroid hormone production. In particular, we discuss the structure and function of SR-BI, the importance of the selective cholesterol transport pathway in providing cholesterol substrate for steroid biosynthesis and the role of two key proteins, StAR and PBR/TSO in facilitating cholesterol delivery to inner mitochondrial membrane sites, where P450scc (CYP11A is localized and where the conversion of cholesterol to

  10. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.

    2013-01-01

    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  11. Transintestinal cholesterol efflux

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Brufau, Gemma; Groen, Albert K.

    2010-01-01

    Purpose of review Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding

  12. Cholesterol: Up in Smoke.

    Science.gov (United States)

    Raloff, Janet

    1991-01-01

    Discussed is the contribution cooked meat makes to air pollution. The dozens of compounds, including cholesterol, that are released when a hamburger is grilled are described. The potential effects of these emissions on humans and the urban environment are discussed. (KR)

  13. Isolation of low density lipoprotein (LDL with its modification by Copper ion and Malondialdehyde (MDA

    Directory of Open Access Journals (Sweden)

    Doosty M

    1999-06-01

    Full Text Available Oxidation of low density lipoproteins (LDLs is belived to be an important step in the pathogenesis of atherosclerosis. During oxidation, LDL particle undergoes a large number of structural changes that alters its biological properties, so it becomes atherogenic. To study atherogenic proteins, usually two forms of modified LDLs, including Cu2+-oxidized LDL (ox-LDL and malondialdehyde (MDA modified LDL (mal-LDL are used. In this study, LDL was isolated from 72 ml freshly prepared plasma by sequential Floatation Ultracentrifugation (SFU, which resulted in separation of 12.5 mg LDL protein. LDL oxidation was accomplished in Phosphate Buffered Saline (PBS with 2µM cupric sulfate, and mal-LDL was prepared by incubating LDL in PBS with 0.5 M solution of freshly prepared MDA. These modifications were evaluated by measuring optical density at 234 nm, Thiobarbitoric Acid Reactive Substances (TBARS, and electrophoretic mobility at pH 8.6. The increase of 234 nm absorption reflected initiation of LDL oxidation. TBARS of ox-LDL and mal-LDL was 80 Nm MAD/mg LDL protein and 400 nm MDA/mg LDL protein, respectively. Electrophoretic mobility of ox-LDL and mal-LDL, in respect to native LDL (n-LDL, were increased.

  14. NMR and interval PLS as reliable methods for determination of cholesterol in rodent lipoprotein fractions

    DEFF Research Database (Denmark)

    Kristensen, Mette; Savorani, Francesco; Ravn-Haren, Gitte

    2010-01-01

    Risk of cardiovascular disease is related to cholesterol distribution in different lipoprotein fractions. Lipoproteins in rodent model studies can only reliably be measured by time- and plasma-consuming fractionation. An alternative method to measure cholesterol distribution in the lipoprotein...... data and the NMR spectra, an interval partial least-square (iPLS) regression model to predict the amount of cholesterol in the different lipoprotein fractions was developed. The relative errors of the prediction models were between 12 and 33% and had correlation coefficients (r) between 0.96 and 0.......84. The models were tested with an independent test set giving prediction errors between 19 and 46% and r between 0.96 and 0.76. Prediction of High, Low and Very Low Density Lipoprotein (HDL, LDL and VLDL) and total cholesterol was conducted in a study where rats had been supplemented with two doses of air...

  15. Monounsaturated oils do not all have the same effect on plasma cholesterol.

    Science.gov (United States)

    Truswell, A S; Choudhury, N

    1998-05-01

    Evidence assembled here indicates that when olive oil forms a major part of dietary fat in controlled human experiments, total and LDL-cholesterols are somewhat higher than when the same amount of fat is one of the modern predominantly monounsaturated oils: low erucic rapeseed or high oleic sunflower oil. Oils rich in monounsaturated fatty acids thus do not all have the same effect on plasma cholesterol. This phenomenon is explicable by consideration of the content of other fatty acids and the non-saponifiable fractions of the different monounsaturated oils. It helps to explain the discrepancy that has existed between the classic experiments (using olive oil), which found monounsaturated oils 'neutral', and some of the more recent experiments which found them more cholesterol-lowering than carbohydrates. Four published meta-analyses are reviewed. The three which included most of the published experiments show that monounsaturated fatty acids (MUFA) have less plasma cholesterol-lowering effect than polyunsaturated fatty acids.

  16. Cholesterol transport in model membranes

    Science.gov (United States)

    Garg, Sumit; Porcar, Lionel; Butler, Paul; Perez-Salas, Ursula

    2010-03-01

    Physiological processes distribute cholesterol unevenly within the cell. The levels of cholesterol are maintained by intracellular transport and a disruption in the cell's ability to keep these normal levels will lead to disease. Exchange rates of cholesterol are generally studied in model systems using labeled lipid vesicles. Initially donor vesicles have all the cholesterol and acceptor vesicles are devoid of it. They are mixed and after some time the vesicles are separated and cholesterol is traced in each vesicle. The studies performed up to date have significant scatter indicating that the methodologies are not consistent. The present work shows in-situ Time-Resolved SANS studies of cholesterol exchange rates in unsaturated PC lipid vesicles. Molecular dynamics simulations were done to investigate the energetic and kinetic behavior of cholesterol in this system. This synergistic approach will provide insight into our efforts to understand cholesterol traffic.

  17. Triterpenic Acids Present in Hawthorn Lower Plasma Cholesterol by Inhibiting Intestinal ACAT Activity in Hamsters

    Directory of Open Access Journals (Sweden)

    Yuguang Lin

    2011-01-01

    Full Text Available Hawthorn (Crataegus pinnatifida is an edible fruit used in traditional Chinese medicine to lower plasma lipids. This study explored lipid-lowering compounds and underlying mechanisms of action of hawthorn. Hawthorn powder extracts inhibited acylCoA:cholesterol acyltransferase (ACAT activity in Caco-2 cells. The inhibitory activity was positively associated with triterpenic acid (i.e., oleanolic acid (OA and ursolic acid (UA contents in the extracts. Cholesterol lowering effects of hawthorn and its potential additive effect in combination with plant sterol esters (PSE were further studied in hamsters. Animals were fed a semi-synthetic diet containing 0.08% (w/w cholesterol (control or the same diet supplemented with (i 0.37% hawthorn dichloromethane extract, (ii 0.24% PSE, (iii hawthorn dichloromethane extract (0.37% plus PSE (0.24% or (iv OA/UA mixture (0.01% for 4 weeks. Compared to the control diet, hawthorn, PSE, hawthorn plus PSE and OA/UA significantly lowered plasma non-HDL (VLDL + LDL cholesterol concentrations by 8%, 9%, 21% and 6% and decreased hepatic cholesterol ester content by 9%, 23%, 46% and 22%, respectively. The cholesterol lowering effects of these ingredients were conversely associated with their capacities in increasing fecal neutral sterol excretion. In conclusion, OA and UA are responsible for the cholesterol lowering effect of hawthorn by inhibiting intestinal ACAT activity. In addition, hawthorn and particularly its bioactive compounds (OA and UA enhanced the cholesterol lowering effect of plant sterols.

  18. Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.

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    Nabil G Seidah

    Full Text Available Proprotein convertase subtilisin/kexin-9 (PCSK9 enhances the degradation of hepatic low-density lipoprotein receptor (LDLR. Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2 as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/- mice revealed: i a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/- tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.

  19. Beneficial effect of low dose Amlodipine vs Nifedipine on serum cholesterol profile of rabbits receiving standard diet.

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    Bavane DS, Rajesh CS, Gurudatta Moharir, Bharatha Ambadasu

    2013-01-01

    Full Text Available To investigate the effect of low dose amlodipine v/s nifedipine on serum cholesterol profile of rabbits receiving standard diet. Methods: Fourty Newzealand rabbits were selected for the study. Their cholesterol profile was estimated at the beginning of the study. Rabbits were grouped into 4 groups receiving standard diet (control group, standard diet + vehicle propylene glycol, standard diet + nifedipine dissolved in propylene glycol and standard diet + amlodipine dissolved in propylene glycol. Along with standard diet they were treated with respective drugs for ten weeks. At the end of ten weeks serum cholesterol profile was estimated. Results: The cholesterol profile was estimated at the beginning and at the end of ten weeks. Total cholesterol in the amlodipine group decreased from 97±4.06 mg/dl to 90±4.2 mg/dl and HDL-Cholesterol increased from 32.01±4.40 mg/dl to 37±4.60 mg/dl after 10 week treatment but these changes were not significant. LDL cholesterol decreased significantly in rabbits with low dose of amlodipine from 55.42±3.32 mg/dl to 32.40±3.22 mg/dl and. In the nifedipine group there was a slight increase in total cholesterol from 102.49±5.16 mg/dl to 106±5.39 mg/dl, HDL cholesterol from 34.10±2.80 to 35.16±2.82 mg/dl and LDL cholesterol also increased from 56.20±2.20 mg/dl to 59.00±2.20 mg/dl after 10 week treatment. Conclusion: The study shows amlodipine produces favorable alterations in serum cholesterol profile

  20. Macrophage-specific overexpression of interleukin-5 attenuates atherosclerosis in LDL receptor-deficient mice.

    Science.gov (United States)

    Zhao, W; Lei, T; Li, H; Sun, D; Mo, X; Wang, Z; Zhang, K; Ou, H

    2015-08-01

    Interleukin-5 (IL-5) increases the secretion of natural T15/EO6 IgM antibodies that inhibit the uptake of oxidized low-density lipoprotein (LDL) by macrophages. This study aimed to determine whether macrophage-specific expression of IL-5 in LDL receptor-deficient mice (Ldlr(-/-)) could improve cholesterol metabolism and reduce atherosclerosis. To induce macrophage-specific IL-5 expression, the pLVCD68-IL5 lentivirus was delivered into Ldlr(-/-) mice via bone marrow transplantation. The recipient mice were fed a Western-type diet for 12 weeks to induce lesion formation. We found that IL-5 was efficiently and specifically overexpressed in macrophages in recipients of pLVCD68-IL5-transduced bone marrow cells (BMC). Plasma titers of T15/EO6 IgM antibodies were significantly elevated by 58% compared with control mice transplanted with pLVCD68 lacking the IL-5 coding sequence. Plaque areas of aortas in IL-5-overexpressing mice were reduced by 43% and associated with a 2.4-fold decrease in lesion size at the aortic roots when compared with mice receiving pLVCD68-transduced BMCs. The study showed that macrophage-specific overexpression of IL-5 inhibited the progression of atherosclerotic lesions. These findings suggest that modulation of IL-5 cytokine expression represents a potential strategy for intervention of familial hypercholesterolemia and other cardiovascular diseases.

  1. Cholesterol excretion and colon cancer.

    Science.gov (United States)

    Broitman, S A

    1981-09-01

    Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.

  2. Differential regulation of acid sphingomyelinase in macrophages stimulated with oxidized low-density lipoprotein (LDL) and oxidized LDL immune complexes: role in phagocytosis and cytokine release.

    Science.gov (United States)

    Truman, Jean-Philip; Al Gadban, Mohammed M; Smith, Kent J; Jenkins, Russell W; Mayroo, Nalini; Virella, Gabriel; Lopes-Virella, Maria F; Bielawska, Alicja; Hannun, Yusuf A; Hammad, Samar M

    2012-05-01

    Oxidized low-density lipoprotein (oxLDL) and oxLDL-containing immune complexes (oxLDL-IC) contribute to the formation of lipid-laden macrophages (foam cells). Fcγ receptors mediate uptake of oxLDL-IC, whereas scavenger receptors internalize oxLDL. We have previously reported that oxLDL-IC, but not free oxLDL, activate macrophages and prolong their survival. Sphingomyelin is a major constituent of cell membranes and lipoprotein particles and acid sphingomyelinase (ASMase) hydrolyses sphingomyelin to generate the bioactive lipid ceramide. ASMase exists in two forms: lysosomal (L-ASMase) and secretory (S-ASMase). In this study we examined whether oxLDL and oxLDL-IC regulate ASMase differently, and whether ASMase mediates monocyte/macrophage activation and cytokine release. The oxLDL-IC, but not oxLDL, induced early and consistent release of catalytically active S-ASMase. The oxLDL-IC also consistently stimulated L-ASMase activity, whereas oxLDL induced a rapid transient increase in L-ASMase activity before it steadily declined below baseline. Prolonged exposure to oxLDL increased L-ASMase activity; however, activity remained significantly lower than that induced by oxLDL-IC. Further studies were aimed at defining the function of the activated ASMase. In response to oxLDL-IC, heat-shock protein 70B' (HSP70B') was up-regulated and localized with redistributed ASMase in the endosomal compartment outside the lysosome. Treatment with oxLDL-IC induced the formation and release of HSP70-containing and IL-1β-containing exosomes via an ASMase-dependent mechanism. Taken together, the results suggest that oxLDL and oxLDL-IC differentially regulate ASMase activity, and the pro-inflammatory responses to oxLDL-IC are mediated by prolonged activation of ASMase. These findings may contribute to increased understanding of mechanisms mediating macrophage involvement in atherosclerosis.

  3. Community-wide survey of physicians' knowledge of cholesterol management

    Institute of Scientific and Technical Information of China (English)

    GUAN Fei; XIE Jiang; WANG Gui-lian; WANG Jia-hong; WANG Jin-song; YU Jin-ming; HU Da-yi

    2010-01-01

    Background An elevated serum lipid is one of the major risk factors for coronary heart disease (CHD). Physicians' awareness contributes to successful adoption of practice guidelines. Community medical centers are the primary defense against chronic disease. This study aimed to investigate community physicians' awareness of cholesterol guidelines and their utilization.Methods Six hundred and one community physicians were randomly selected from four different regions, and completed a confidential and semi-structured questionnaire. Four hundred and ninety-one completed the questionnaire, and 486 valid questionnaires were available.Results The physicians' fundamental knowledge of lipids was astonishingly poor, while the awareness of cholesterol guidelines was low. Only 24% and 14% of the physicians reported the right optimal low-density lipoprotein cholesterol (LDL-C) level for CHD and diabetes patients respectively. More than half of the physicians (55.8%) mistakenly considered elevated transaminases to be the lethal side effect of statins. More than half of the physicians (51.9%) would give up statin treatment in the case of transaminase elevation.Conclusion Educational interventions to improve cholesterol knowledge and to publicize standard treatment are needed among Chinese community physicians.

  4. Small dense LDL particles - a predictor of coronary artery disease evaluated by invasive and CT-based techniques: a case-control study

    Directory of Open Access Journals (Sweden)

    Andreasen Annette

    2011-01-01

    Full Text Available Abstract Background Coronary angiography is the current standard method to evaluate coronary atherosclerosis in patients with suspected angina pectoris, but non-invasive CT scanning of the coronaries are increasingly used for the same purpose. Low-density lipoprotein (LDL cholesterol and other lipid and lipoprotein variables are major risk factors for coronary artery disease. Small dense LDL particles may be of particular importance, but clinical studies evaluating their predictive value for coronary atherosclerosis are few. Methods We performed a study of 194 consecutive patients with chest pain, a priori considered of low to intermediate risk for significant coronary stenosis (>50% lumen obstruction who were referred for elective coronary angiography. Plasma lipids and lipoproteins were measured including the subtype pattern of LDL particles, and all patients were examined by coronary CT scanning before coronary angiography. Results The proportion of small dense LDL was a strong univariate predictor of significant coronary artery stenosis evaluated by both methods. After adjustment for age, gender, smoking, and waist circumference only results obtained by traditional coronary angiography remained statistically significant. Conclusion Small dense LDL particles may add to risk stratification of patients with suspected angina pectoris.

  5. Validation of using gene expression in mononuclear cells as a marker for hepatic cholesterol metabolism

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    Dutta Amrita

    2006-08-01

    Full Text Available Abstract HMG-CoA reductase and the LDL receptor are ubiquitously expressed in major tissues. Since the liver plays a major role in regulating circulating LDL, it is usually of interest to measure the effects of drug or dietary interventions on these proteins in liver. In humans, peripheral blood mononuclear cells have been used as a surrogate for liver to assess regulation of these genes, although there is concern regarding the validity of this approach. The purpose of this study was to evaluate the relationship between liver and mononuclear cell expression of HMG-CoA reductase and the LDL receptor in guinea pigs, a well established model for human cholesterol and lipoprotein metabolism. We extracted RNA from liver and mononuclear cells of guinea pigs from a previous study where the effects of rapamycin, an immunosuppresant drug used for transplant patients, on lipid metabolism were evaluated. Guinea pigs were assigned to three different diets containing the same amount of fat (15 g/100 g and cholesterol (0.08 g/100 g for a period of 3 weeks. The only difference among diets was the concentration of rapamycin: 0, 0.0028 or 0.028 g/100 g. There were no differences in plasma LDL cholesterol (LDL-C among groups. Values were 78.4 ± 14.3, 65.8 ± 17.2 and 68.4 ± 45.4 mg/dL (P > 0.05 for guinea pigs treated with 0, low or high doses of rapamycin, respectively. The mRNA abundance for the LDL receptor and HMG-CoA reductase was measured both in liver (n = 30 and mononuclear cells (n = 22 using reverse transcriptase PCR. In agreement with the finding of no changes in plasma LDL-C, there were also no differences for the expression of HMG-CoA reductase or the LDL receptor among groups. However, a positive correlation was found between liver and mononuclear cells for both HMG-CoA reductase (r = 0.613, P

  6. Cholesterol:phospholipid ratio is elevated in platelet plasma membrane in patients with hypertension.

    Science.gov (United States)

    Benjamin, N; Robinson, B F; Graham, J G; Wilson, R B

    1990-06-01

    The cholesterol:phospholipid ratio was measured in platelet plasma membrane, red blood cell (RBC) membranes, low density lipoprotein (LDL) and whole plasma in patients with primary hypertension and in matched normal controls. The cholesterol:phospholipid ratio was raised in the platelet membrane from hypertensive patients compared with that from normal controls (0.65 +/- 0.03 vs 0.53 +/- 0.02: mean +/- SEM; P less than 0.01). The ratio observed in RBC membranes, LDL and whole blood was similar in the two groups. If this abnormality in the lipid composition of platelet plasma membrane is present in other cells it could account for some of the changes in cell membrane function that have been described in hypertension.

  7. 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.

  8. Arctigenin promotes cholesterol efflux from THP-1 macrophages through PPAR-γ/LXR-α signaling pathway.

    Science.gov (United States)

    Xu, Xiaolin; Li, Qian; Pang, Liewen; Huang, Guoqian; Huang, Jiechun; Shi, Meng; Sun, Xiaotian; Wang, Yiqing

    2013-11-15

    Cholesterol efflux from macrophages is a critical mechanism to prevent the development of atherosclerosis. Here, we sought to investigate the effects of arctigenin, a bioactive component of Arctium lappa, on the cholesterol efflux in oxidized low-density lipoprotein (oxLDL)-loaded THP-1 macrophages. Our data showed that arctigenin significantly accelerated apolipoprotein A-I- and high-density lipoprotein-induced cholesterol efflux in both dose- and time-dependent manners. Moreover, arctigenin treatment enhanced the expression of ATP binding cassette transporter A1 (ABCA1), ABCG1, and apoE, all of which are key molecules in the initial step of cholesterol efflux, at both mRNA and protein levels. Arctigenin also caused a concentration-dependent elevation in the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and liver X receptor-alpha (LXR-α). The arctigenin-mediated induction of ABCA1, ABCG1, and apoE was abolished by specific inhibition of PPAR-γ or LXR-α using small interfering RNA technology. Our results collectively indicate that arctigenin promotes cholesterol efflux in oxLDL-loaded THP-1 macrophages through upregulation of ABCA1, ABCG1 and apoE, which is dependent on the enhanced expression of PPAR-γ and LXR-α.

  9. Effects of plant sterols and stanols on intestinal cholesterol metabolism: suggested mechanisms from past to present.

    Science.gov (United States)

    De Smet, Els; Mensink, Ronald P; Plat, Jogchum

    2012-07-01

    Plant sterols and stanols are natural food ingredients found in plants. It was already shown in 1950 that they lower serum low-density lipoprotein cholesterol (LDL-C) concentrations. Meta-analysis has reported that a daily intake of 2.5 g plant sterols/stanols reduced serum LDL-C concentrations up to 10%. Despite many studies, the underlying mechanism remains to be elucidated. Therefore, the proposed mechanisms that have been presented over the past decades will be described and discussed in the context of the current knowledge. In the early days, it was suggested that plant sterols/stanols compete with intestinal cholesterol for incorporation into mixed micelles as well as into chylomicrons. Next, the focus shifted toward cellular processes. In particular, a role for sterol transporters localized in the membranes of enterocytes was suggested. All these processes ultimately lowered intestinal cholesterol absorption. More recently, the existence of a direct secretion of cholesterol from the circulation into the intestinal lumen was described. First results in animal studies suggested that plant sterols/stanols activate this pathway, which also explains the increased fecal neutral sterol content and as such could explain the cholesterol-lowering activity of plant sterols/stanols.

  10. Influence factors of success rate of serum LDL-C in patients with unstability angina pectoris taking atorvastatin%服用阿托伐他汀的不稳定型心绞痛患者血清LDL-C达标率的影响因素

    Institute of Scientific and Technical Information of China (English)

    于薇; 孟存良; 容春莉; 曹东平; 吕军娥; 彭应心

    2011-01-01

    目的 分析使用阿托伐他汀的不稳定型心绞痛患者低密度脂蛋白胆固醇(LDL-C)达标率的临床影响因素.方法 选择血清LDL-C水平未达标的不稳定型心绞痛患者146例,阿托伐他汀20 mg口服,1次/d,疗程8周.分析年龄、性别、体质量指数(BMI)、膳食控制、糖基化血红蛋白A1c(HbA1c)等因素对服用阿托伐他汀后LDL-C达标率的影响.结果服用阿托伐他汀8周后,LDL-C总达标率为49.3%;经逐步多元Logistic回归分析,年龄与LDL-C达标率无显著相关性;BMI正常组、超体质量组和肥胖组的组间比较,LDL-C达标率差异无统计学意义(P>0.05);膳食控制组较无膳食控制组患者LDL-C达标率高;血糖控制良好的患者LDL-C达标率高.结论 膳食及血糖控制水平为服用阿托伐他汀的不稳定型心绞痛患者LDL-C达标率的独立影响因素.%Objective To analyze the clinical influence factors of success rate of serum low density lipoprotein-cholesterol(LDL-C) in patients with unstability angina pectoris taking aorvastatin. Methods 146 patients with unstability angina pectoris and unsuccessful level of serum LDL-C were collected. 20 mg atorvastatin were taken orally once a day with treatment course of 8 weeks.Effects of clinical factors such as age, gender, body mass index(BMI), diet control and glycosylated hemoglobin Alc (HbAlc) on success rate of serum LDL-C after aorvastatin administration were analyzed. Results The overall success rate of serum LDL-C was 49.3 % after 8 weeks of aorvastatin administration;Age had no significant correlation with the success rate of LDL-C according to stepwise multivariate Logistic regression analysis;Comparison of the success rates of LDL-C among BMI normal group,overweight group and obesity group,there were no statistically significant(P>0.05) ;Success rates of LDL-C of patients in diet control group were higher than that in non-diet control group;Patients with well-controlled blood glucose showed

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

    Science.gov (United States)

    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 treatment targets with statins. Therefore, an unmet medical need exists for lipid-lowering drugs with novel mechanisms of action to reach the recommended cholesterol target levels, either by monotherapy or combination therapy. Upregulation of the LDL receptor with squalene synthase inhibitors has shown promising results in animal studies but the clinical development of the lead compound lapaquistat (TAK-475) has recently been discontinued. Ezetimibe combined with statins allowed significantly more patients to reach their LDL-C targets. Other inhibitors of intestinal cholesterol absorption such as disodium ascorbyl phytostanol phosphate (FM-VP4) and bile acid transport inhibitors have shown positive results in early development trials, whereas the prospect of acyl coenzyme A: cholesterol acyltransferase inhibition in cardiovascular prevention is dire. Selective inhibition of messenger RNA (mRNA) by antisense oligonucleotides is a new approach to modify cholesterol levels. The inhibition of apolipoprotein B mRNA is in advanced development and mipomersen sodium (ISIS 301012) has shown striking results in phase II studies both as monotherapy as well as in combination with statins.

  12. How to Get Your Cholesterol Tested

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More How To Get Your Cholesterol Tested Updated:Apr 3,2017 Cholesterol plays a ... factors for heart disease and stroke . How is cholesterol tested? A cholesterol screening measures your level of ...

  13. Improving glycemic and cholesterol control through an integrated approach incorporating colesevelam – a clinical perspective

    Directory of Open Access Journals (Sweden)

    Ronald B Goldberg

    2009-05-01

    Full Text Available Ronald B GoldbergDivision of Endocrinology, Diabetes and Metabolism, Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USAAbstract: Bile sequestrants have been used for almost 50 years to lower low density lipoprotein cholesterol (LDL-C. The advent of colesevelam in 2000 provided a more tolerable add-on LDL-C-lowering agent with an excellent safety record and with likely benefit for coronary heart disease events. Colesevelam lowers LDL-C approximately 15%, and has an additive effect when combined with statin or non-statin lipid-modifying agents. It also tends to increase triglyceride levels. The discovery that bile sequestrants also lower glucose levels led to definitive large-scale clinical trials testing the effect of colesevelam as a dual antihyperglycemic agent with LDL-C-lowering properties in type 2 diabetic subjects on metformin-, sulfonylurea- or insulin-based therapy with inadequate glycemic control. Colesevelam was found to lower hemoglobin A1c (HbA1c by approximately 0.5% compared to placebo over the 16- to 26-week period, and had similar effects on the lipid profile in these diabetic subjects, as had previously been demonstrated in non-diabetic individuals. Colesevelam was well tolerated, with constipation being the most common adverse effect, and did not cause weight gain or excessive hypoglycemia. Colesevelam thus combines antihyperglycemic action with LDL-C-lowering properties, and should be useful in the management of type 2 diabetes.Keywords: colesevelam, treatment, hyperglycemia, LDL-cholesterol

  14. ROCK2 associates with lectin-like oxidized LDL receptor-1 and mediates oxidized LDL-induced IL-8 production.

    Science.gov (United States)

    Mattaliano, Mark D; Wooters, Joe; Shih, Heather H; Paulsen, Janet E

    2010-05-01

    Oxidatively modified low-density lipoprotein (OxLDL) is a contributing factor of endothelial dysfunction, an early cellular event during atherogenesis. In endothelial cells, OxLDL has been shown to stimulate proinflammatory responses, increase lipid accumulation, and induce the expression of adhesion and extracellular matrix degrading molecules. The primary receptor for OxLDL on endothelial cells has been identified as a member of the scavenger receptor family called lectin-like OxLDL receptor-1 (LOX-1). A number of studies on LOX-1 have implicated its role in multiple cardiovascular diseases including atherosclerosis. To better understand the molecular mechanisms underlying the role of LOX-1 in endothelial cells, we identified interacting proteins in an affinity-purified LOX-1 receptor complex from human aortic endothelial HAECT cells by mass spectrometry. Two molecules involved in Rho signaling pathway, ARHGEF1 and ROCK2, were identified, and their associations with LOX-1 were confirmed in reciprocal immunoprecipitation studies. Particularly, ROCK2 was found to dynamically associate with LOX-1 in the presence of OxLDL. In addition, OxLDL treatment stimulated ROCK2 catalytic activity, and ROCK2 inhibition attenuated NF-kappaB activation and IL-8 production resulting from OxLDL activation of LOX-1. In summary, a functional proteomics approach has enabled us to identify novel LOX-1 interactors that potentially contribute to the cellular and signaling functions of LOX-1.

  15. Concentrated oat β-glucan, a fermentable fiber, lowers serum cholesterol in hypercholesterolemic adults in a randomized controlled trial

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    Fulcher R Gary

    2007-03-01

    Full Text Available Abstract Background Soluble fibers lower serum lipids, but are difficult to incorporate into products acceptable to consumers. We investigated the physiological effects of a concentrated oat β-glucan on cardiovascular disease (CVD endpoints in human subjects. We also compared the fermentability of concentrated oat β-glucan with inulin and guar gum in a model intestinal fermentation system. Methods Seventy-five hypercholesterolemic men and women were randomly assigned to one of two treatments: 6 grams/day concentrated oat β-glucan or 6 grams/day dextrose (control. Fasting blood samples were collected at baseline, week 3, and week 6 and analyzed for total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, glucose, insulin, homocysteine and C-reactive protein (CRP. To estimate colonic fermentability, 0.5 g concentrated oat β-glucan was incubated in a batch model intestinal fermentation system, using human fecal inoculum to provide representative microflora. Fecal donors were not involved with the β-glucan feeding trial. Inulin and guar gum were also incubated in separate serum bottles for comparison. Results Oat β-glucan produced significant reduction from baseline in total cholesterol (-0.3 ± 0.1 mmol/L and LDL cholesterol (-0.3 ± 0.1 mmol/L, and the reduction in LDL cholesterol were significantly greater than in the control group (p = 0.03. Concentrated oat β-glucan was a fermentable fiber and produced total SCFA and acetate concentrations similar to inulin and guar gum. Concentrated oat β-glucan produced the highest concentrations of butyrate at 4, 8, and 12 hours. Conclusion Six grams concentrated oat β-glucan per day for six weeks significantly reduced total and LDL cholesterol in subjects with elevated cholesterol, and the LDL cholesterol reduction was greater than the change in the control group. Based on a model intestinal fermentation, this oat β-glucan was fermentable, producing higher amounts of butyrate than other

  16. EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of a health claim related to barley beta-glucan and lowering of blood cholesterol and reduced risk of (coronary) heart disease pursuant to Article 14 of Regulation (EC) No 1924/2006

    DEFF Research Database (Denmark)

    Tetens, Inge

    -glucans, is sufficiently characterised. Lowering blood LDL-cholesterol concentration is a beneficial physiological effect by decreasing the risk of coronary heart disease. The applicant identified a total of 16 references as being pertinent to the health claim. These references comprised three meta-analyses, 10 human...... intervention studies, two animal studies and one mechanistic study. In weighing the evidence, the Panel took into account that one meta-analysis including 11 RCTs and one additional RCT which investigated the effects of barley beta-glucans at doses of at least 3 g/day showed a decrease in total and LDL-cholesterol...... the consumption of barley beta-glucans and the lowering of blood LDL-cholesterol concentrations. The following wording reflects the scientific evidence: “Barley beta-glucans have been shown to lower/reduce blood cholesterol. High cholesterol is a risk factor in the development of coronary heart disease”. At least...

  17. Natural Honey and Cardiovascular Risk Factors; Effects on Blood Glucose, Cholesterol, Triacylglycerole, CRP, and Body Weight Compared with Sucrose

    Directory of Open Access Journals (Sweden)

    N. Yaghoobi

    2008-01-01

    Full Text Available It has been found that honey ameliorates cardiovascular risk factors in healthy individuals and in patients with elevated risk factors. The present study investigated the effect of natural honey on total cholesterol, low-density lipoprotein cholesterol (LDL-C, high-density lipoprotein cholesterol (HDL-C, triacylglycerole, C-reactive protein (CRP, fasting blood glucose (FBG, and body weight in overweight individuals. There were 55 patients, overweight or obese, who were randomly recruited into the study and assigned into two groups: control group (17 subjects and experimental group (38 subjects. Patients in the control group received 70 g of sucrose daily for a maximum of 30 days and patients in the experimental group received 70 g of natural honey for the same period. In the control and experimental groups, body weight, body mass index, body fat weight, total cholesterol, LDL-C, HDL-C, triacylglycerole, FBG, and CRP were measured before treatment and at day 31 after the commencement of treatment. Results showed that honey caused a mild reduction in body weight (1.3% and body fat (1.1%. Honey reduced total cholesterol (3%, LDL-C (5.8, triacylglycerole (11%, FBG (4.2%, and CRP (3.2%, and increased HDL-C (3.3% in subjects with normal values, while in patients with elevated variables, honey caused reduction in total cholesterol by 3.3%, LDL-C by 4.3%, triacylglycerole by 19%, and CRP by 3.3% (p < 0.05. It is our conclusion that consumption of natural honey reduces cardiovascular risk factors, particularly in subjects with elevated risk factors, and it does not increase body weight in overweight or obese subjects.

  18. Serum TC/HDL-C,TG/HDL-C and LDL-C/HDL-C in predicting the risk of myocardial infarction in normolipidae-mic patients in South Asia:A case-control study

    Institute of Scientific and Technical Information of China (English)

    Arun Kumar; Ramiah Sivakanesan

    2008-01-01

    Dyslipidemia the major cause of atherosclerosis are suggested to act synergistically with non-lipid risk factors to increase atherogenesis.Low-density lipoprotein cholesterol (LDL-C)is the main therapeutic target in the pre-vention of CVD.Increased triglycerides (TG)and decreased high-density lipoprotein (LDL-C)are considered to be a major risk factor for the development of insulin resistant and metabolic syndrome.Although the TG/HDL-C ratio has been used in recent studies as a clinical indicator for insulin resistance,results were inconsis-tent.The TG/HDL-C ratio is also widely used to assess the lipid atherogenesis.How ever the utility of this rate for predicting coronary heart disease (CHD)risk is not clear.We encountered myocardial infarct patients with normal serum lipid concentration so this study was undertaken to evaluate the usefulness of these lipid ratios in predicting CHD risk in normolipidemic AMI patients and to compare the results with healthy subjects.The aim of the present study was to evaluate serum TC/HDL-C,TG/HDL-C and LDL-C/HDL-C in myocardial infarct subjects with normal lipid profile.To study this,lipid profile was determined in 165 normolipidemic acute myo-cardial infarction patients and 165 age/sex-matched controls.Total cholesterol,triglycerides,and HDL-cho-lesterol were analyzed enzymatically using kits obtained from Randox Laboratories Limited,Crumlin,UK. Plasma LDL-cholesterol was determined from the values of total cholesterol and HDL- cholesterol using the friedwalds formula.The values were expressed as means ± standard deviation (SD)and data from patients and controls was compared using students't'-test.The results and conclusion of the study were:Total cholester-ol,TC:HDL-C ratio,triglycerides,LDL-cholesterol,LDL:HDL-C ratio were higher in MI patients (p<0. 001).HDL-C concentration was significantly lower in MI patients than controls (p<0.001).Higher ratio of TC/HDL-C,TG/HDL-C and LDL-C/HDL-C was observed in AMI patients compared

  19. Cholesterol-lowering interventions and stroke: Insights from IMPROVE-IT.

    Science.gov (United States)

    De Caterina, Raffaele; Salvatore, Tanya; Marchioli, Roberto

    2016-05-01

    The relationship of cholesterol with stroke is much less clear than its relationship with myocardial infarction, thus confounding the interpretation of results with cholesterol-lowering trials. Because for long time the only lipid-lowering intervention reducing stroke was statins, it has been actually argued that reduction in stroke found in statin trials is not due to statins' ability to reduce LDL cholesterol, but to other "pleiotropic" effects, unrelated to cholesterol lowering. In re-analyzing the relationship of cholesterol lowering versus changes in the risk of stroke in a meta-regression of all cholesterol-lowering interventions, including also non-statin interventions, we had previously reached the opposite conclusion: that some reduction in stroke has to be expected proportional to cholesterol reduction. We had predicted that a 1% reduction of total cholesterol-no matter by what intervention produced-was associated with a 0.8% relative risk reduction of stroke. Data from the recently published Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) now offer a clear proof of this concept, demonstrating that pure cholesterol lowering, as obtained with ezetimibe, plays an important role in reducing stroke. IMPROVE-IT data, showing a 13.3% reduction in total cholesterol at one year in association with a hazard ratio (HR) of 0.86 for total stroke during the trial, are very closely aligned with the relative risk of 0.90 predicted on the basis of the totality of lipid lowering interventions. These data are important to predict stroke outcomes in currently ongoing trials now testing PCSK9 or cholesterol ester transfer protein inhibitors.

  20. Cholesterol crystal embolism (atheroembolism)

    Science.gov (United States)

    VENTURELLI, CHIARA; JEANNIN, GUIDO; SOTTINI, LAURA; DALLERA, NADIA; SCOLARI, FRANCESCO

    2006-01-01

    Cholesterol crystal embolism, known as atheroembolic disease, is caused by showers of cholesterol crystals from an atherosclerotic plaque that occludes small arteries. Embolization can occur spontaneously or as an iatrogenic complication from an invasive vascular procedure (angiography or vascular surgery) and after anticoagulant therapy. The atheroembolism can give rise to different degrees of renal impairment. Some patients show a moderate loss of renal function, others severe renal failure requiring dialysis. Renal outcome can be variable: some patients deteriorate or remain on dialysis, some improve and some remain with chronic renal impairment. Clinically, three types of atheroembolic renal disease have been described: acute, subacute or chronic. More frequently a progressive loss of renal function occurs over weeks. Atheroembolization can involve the skin, gastrointestinal system and central nervous system. The diagnosis is difficult and controversial for the protean extrarenal manifestations. In the past, the diagnosis was often made post-mortem. In the last 10 yrs, awareness of atheroembolic renal disease has improved. The correct diagnosis requires the clinician to be alert. The typical patient is a white male aged >60 yrs with a history of hypertension, smoking and arterial disease. The presence of a classic triad (precipitating event, renal failure and peripheral cholesterol crystal embolization) suggests the diagnosis. This can be confirmed by a biopsy of the target organs. A specific treatment is lacking; however, it is an important diagnosis to make because an aggressive therapeutic approach can be associated with a more favorable clinical outcome. PMID:21977265

  1. Effect of Ezetimibe on LDL-C Lowering and Atherogenic Lipoprotein Profiles in Type 2 Diabetic Patients Poorly Controlled by Statins.

    Directory of Open Access Journals (Sweden)

    Kentaro Sakamoto

    Full Text Available There exists a subpopulation of T2DM in whom first-line doses of statin are insufficient for optimally reducing LDL-C, representing a major risk of CVD. The RESEARCH study focuses on LDL-C reduction in this population along with modifications of the lipid profiles leading to residual risks.Lipid changes were assessed in a randomized, multicenter, 12-week, open-label study comparing a high-potency statin (10mg of atorvastatin or 1mg of pitavastatin plus ezetimibe (EAT: n = 53 with a double dose of statin (20mg of atorvastatin or 2mg of pitavastatin (DST: n = 56 in DM subjects who had failed to achieve the optimal LDL-C targets. Lipid variables were compared with a primary focus on LDL-C and with secondary focuses on the percentage of patients who reached the LDL-C targets and changes in the levels of RLP-C (remnant like particle cholesterol and sd-LDL-C, two characteristic atherogenic risks of DM.The reduction of LDL-C (%, the primary endpoint, differed significantly between the two groups (-24.6 in EAT vs. -10.9 in DST. In the analyses of the secondary endpoints, EAT treatment brought about significantly larger reductions in sd-LDL-C (-20.5 vs. -3.7 and RLP-C (-19.7 vs. +5.5. In total, 89.4% of the patients receiving EAT reached the optimized treatment goal compared to 51.0% of the patients receiving DST. The changes in TC (-16.3 vs. -6.3 and non-HDL-C (-20.7 vs. -8.3 differed significantly between the two groups.Ezetimibe added to high-potency statin (10 mg of atorvastatin or 1 mg of pitavastatin was more effective than the intensified-dose statin (20 mg of atorvastatin or 2 mg of pitavastatin treatment not only in helping T2DM patients attain more LDL-C reduction, but also in improving their atherogenic lipid profiles, including their levels of sd-LDL-C and RLP-C. We thus recommend the addition of ezetimibe to high-potency statin as a first line strategy for T2DM patients with insufficient statin response.The UMIN Clinical Trials Registry UMIN

  2. HDL cholesterol and residual risk of first cardiovascular events after treatment with potent statin therapy: an analysis from the JUPITER trial

    DEFF Research Database (Denmark)

    Ridker, P.M.; Genest, J.; Boekholdt, S.M.;

    2010-01-01

    Background HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Methods...... Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated...... by a computer-generated sequence to receive rosuvastatin 20 mg per day or placebo, with participants and adjudicators masked to treatment assignment. In the present analysis, we divided the participants into quartiles of HDL-cholesterol or apolipoprotein A1 and sought evidence of association between...

  3. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan

    2014-02-01

    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  4. LDL biochemical modifications: a link between atherosclerosis and aging

    Directory of Open Access Journals (Sweden)

    Matilde Alique

    2015-12-01

    Full Text Available Atherosclerosis is an aging disease in which increasing age is a risk factor. Modified low-density lipoprotein (LDL is a well-known risk marker for cardiovascular disease. High-plasma LDL concentrations and modifications, such as oxidation, glycosylation, carbamylation and glycoxidation, have been shown to be proatherogenic experimentally in vitro and in vivo. Atherosclerosis results from alterations to LDL in the arterial wall by reactive oxygen species (ROS. Evidence suggests that common risk factors for atherosclerosis raise the likelihood that free ROS are produced from endothelial cells and other cells. Furthermore, oxidative stress is an important factor in the induction of endothelial senescence. Thus, endothelial damage and cellular senescence are well-established markers for atherosclerosis. This review examines LDL modifications and discusses the mechanisms of the pathology of atherosclerosis due to aging, including endothelial damage and oxidative stress, and the link between aging and atherosclerosis.

  5. LDL biochemical modifications: a link between atherosclerosis and aging

    Science.gov (United States)

    Alique, Matilde; Luna, Carlos; Carracedo, Julia; Ramírez, Rafael

    2015-01-01

    Atherosclerosis is an aging disease in which increasing age is a risk factor. Modified low-density lipoprotein (LDL) is a well-known risk marker for cardiovascular disease. High-plasma LDL concentrations and modifications, such as oxidation, glycosylation, carbamylation and glycoxidation, have been shown to be proatherogenic experimentally in vitro and in vivo. Atherosclerosis results from alt