Cholesterol Journal Articles

Record 2821 to 2840

Cholesterol reduction in the workplace and in community settings
Wilson, M. G. (1991), J Community Health 16(1): 49-65.
Abstract: Recent emphasis has been placed on the role of serum cholesterol in the development of cardiovascular disease and on reducing high serum cholesterol levels through a screening followed by a behavioral intervention. However, evidence about the effectiveness of this technique in reducing cholesterol has yet to be evaluated. A review of the biomedical and allied health literature was conducted to determine the effectiveness of reducing serum cholesterol levels in the general population through the use of a screening to identify those at risk followed by a behavioral intervention. Only worksite and community based studies published from 1980-89 were reviewed. Seven worksite and four community studies were identified. All studies used total serum cholesterol as the dependent variable while some included other physiological measures. The majority of studies used a multicomponent intervention involving dietary education, exercise, smoking cessation, or weight reduction components. The interventions tested lasted from 14 weeks to five years and varied from low intensity to high intensity. The methods of intervention ranged from face-to-face interaction to mail and telephone counseling. Although many of the studies reviewed contain methodological flaws, certain findings are evident. The studies show that cholesterol can be reduced through a screening followed by a behavioral intervention, the multicomponent program is the most effective intervention, and low intensive interventions are as equally effective as high intensive interventions. Program implications and future research directions are discussed.

Cholesterol reduction rapidly improves endothelial function after acute coronary syndromes. The RECIFE (reduction of cholesterol in ischemia and function of the endothelium) trial
Dupuis, J., J. C. Tardif, et al. (1999), Circulation 99(25): 3227-33.
Abstract: BACKGROUND: Cholesterol lowering reduces coronary events. One mechanism could be improvement of endothelial function. In line with this hypothesis, this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function after acute coronary syndromes. METHODS AND RESULTS: Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission >/=5.2 mmol/L or LDL >/=3.4 mmol/L were randomized to placebo (n=30) or pravastatin 40 mg daily (n=30) for 6 weeks. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation (FMD) and response to endothelium-independent nitroglycerin. Changes in the levels of markers of platelet activation, coagulation factors, and plasma endothelin levels were also assessed. Total and LDL cholesterol levels were similar at admission and before randomization in both groups. With pravastatin, but not with placebo, they decreased by 23% (P<0.05) and 33% (P<0.01), respectively. FMD was unchanged with placebo, 5.43+/-0.74% (mean+/-SEM) to 5.84+/-0.81%, but increased with pravastatin, 4.93+/-0.81% to 7.0+/-0.79% (P=0.02), representing a 42% relative increase. Responses to nitroglycerin were similar during the time course of the study in the 2 groups. Markers of platelet activity, coagulation factors, and endothelin levels were not affected by pravastatin. CONCLUSIONS: Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy.

Cholesterol reduction therapy: a double-edged knife
Ong, H. T. (1993), Med J Malaysia 48(2): 107-12.
Abstract: Cholesterol reduction reduces ischaemic cardiovascular morbidity and mortality in the asymptomatic healthy population as well as in those with known coronary artery disease. Angiographic studies have also demonstrated regression of atherosclerotic plaques as well as retardation of new atheroma formation with such therapy. Yet, there is a consistent inability to reduce overall mortality in cholesterol-lowering drug trials. An excess of suicide, homicide and violence has been attributed to cholesterol reduction interfering with membrane lipids and receptors, leading to aggressive behaviour. The risk and benefits of cholesterol reduction must thus be weighed in the individual patient; it is more useful in those with known coronary artery disease who are at high risk of subsequent ischaemic cardiovascular events.

Cholesterol reduction through low-intensity interventions: results from the Minnesota Heart Health Program
Murray, D. M., C. Kurth, et al. (1990), Prev Med 19(2): 181-9.
Abstract: The National Cholesterol Education Program has underscored the need for health professionals to work together to promote dietary changes and reduce blood cholesterol levels across the population. This article reports the results of an evaluation of several low-intensity intervention programs designed for the general public that could be offered on a larger scale, either through traditional outlets for short courses or on an outpatient basis after physician referral. The interventions were designed as classes, required approximately 8 hr of contact time with the participants, cost approximately $20 per participant, and were taught by nutritionists and dietitians recruited from the community and trained for this program. Results indicated that similar net reductions in total cholesterol of about 4% were achieved at 1-yr follow-up either from a course which focused on changing eating patterns or from one which focused on weight loss and weight-loss management. These results support the hypothesis that cholesterol reduction is possible with inexpensive and simple methods in healthy, low-risk populations.

Cholesterol reduction to prevent CAD. What do the data show?
Sorrentino, M. J. (2000), Postgrad Med 108(7): 40-2, 45-6, 49-52.
Abstract: Primary prevention of heart disease should be an important goal of every primary care physician. All patients should undergo careful assessment of future risk and should be counseled about lifestyle modification. Patients at high risk can further benefit from cautious use of lipid-lowering drugs, which have been shown to be effective in preventing cardiac events without substantially increasing risk of noncardiac morbidity and mortality.

Cholesterol reduction using manufactured foods high in monounsaturated fatty acids: a randomized crossover study
Williams, C. M., J. A. Francis-Knapper, et al. (1999), Br J Nutr 81(6): 439-46.
Abstract: In two separate studies, the cholesterol-lowering efficacy of a diet high in monounsaturated fatty acids (MUFA) was evaluated by means of a randomized crossover trial. In both studies subjects were randomized to receive either a high-MUFA diet or the control diet first, which they followed for a period of 8 weeks; following a washout period of 4-6 weeks they were transferred onto the opposing diet for a further period of 8 weeks. In one study subjects were healthy middle-aged men (n 30), and in the other they were young men (n 23) with a family history of CHD recruited from two centres (Guildford and Dublin). The two studies were conducted over the same time period using identical foods and study designs. Subjects consumed 38% energy as fat, with 18% energy as MUFA and 10% as saturated fatty acids (MUFA diet), or 13% energy as MUFA and 16% as saturated fatty acids (control diet). The polyunsaturated fatty acid content of each diet was 7%. The diets were achieved by providing subjects with manufactured foods such as spreads, 'ready meals', biscuits, puddings and breads, which, apart from their fatty acid compositions, were identical for both diets. Subjects were blind to which of the diets they were following on both arms of the study. Weight changes on the diets were less than 1 kg. In the groups combined (n 53) mean total and LDL-cholesterol levels were significantly lower at the end of the MUFA diet than the control diet by 0.29 (SD 0.61) mmol/l (P < 0.001) and 0.38 (SD 0.64) mmol/l (P < 0.0001) respectively. In middle-aged men these differences were due to a mean reduction in LDL-cholesterol of -11 (SD 12)% on the MUFA diet with no change on the control diet (-1.1 (SD 10)%). In young men the differences were due to an increase in LDL-cholesterol concentration on the control diet of +6.2 (SD 13)% and a decrease on the MUFA diet of -7.8 (SD 20)%. Differences in the responses of middle-aged and young men to the two diets did not appear to be due to differences in their habitual baseline diets which were generally similar, but appeared to reflect the lower baseline cholesterol concentrations in the younger men. There was a moderately strong and statistically significant inverse correlation between the change in LDL-cholesterol concentration on each diet and the baseline fasting LDL-cholesterol concentration (r -0.49; P < 0.0005). In conclusion, diets in which saturated fat is partially replaced by MUFA can achieve significant reductions in total and LDL-cholesterol concentrations, even when total fat and energy intakes are maintained. The dietary approach used to alter fatty acid intakes would be appropriate for achieving reductions in saturated fat intakes in whole populations.

Cholesterol reduction with atorvastatin improves walking distance in patients with peripheral arterial disease
Mohler, E. R., 3rd, W. R. Hiatt, et al. (2003), Circulation 108(12): 1481-6.
Abstract: BACKGROUND: Cholesterol modification reduces cardiovascular events in patients with atherosclerosis, including those with peripheral arterial disease. The purpose of this study was to determine whether cholesterol lowering with atorvastatin improves walking performance in patients with intermittent claudication. METHODS AND RESULTS: This randomized, double-blind, parallel-design study included 354 persons with claudication attributable to peripheral arterial disease. Patients were treated with placebo, atorvastatin (10 mg per day), or atorvastatin (80 mg per day) for 12 months. The outcome measures included change in treadmill exercise time and patient-reported measures of physical activity and quality of life based on questionnaires. Maximal walking time after 12 months of treatment with atorvastatin did not change significantly. However, there was improvement in pain-free walking time after 12 months of treatment for the 80-mg (P=0.025) group compared with placebo. A physical activity questionnaire demonstrated improvement in ambulatory ability for the 10- and 80-mg groups (P=0.011), whereas 2 quality of life instruments, the Walking Impairment Questionnaire and Short Form 36 Questionnaire, did not show significant change. CONCLUSIONS: Atorvastatin improves pain-free walking distance and community-based physical activity in patients with intermittent claudication. When treated with atorvastatin, patients with peripheral arterial disease may experience improvement in symptoms to complement the anticipated reduction in cardiovascular events reported in other studies of statins.

Cholesterol reduction yields clinical benefit. A new look at old data
Gould, A. L., J. E. Rossouw, et al. (1995), Circulation 91(8): 2274-82.
Abstract: BACKGROUND: There has been a continuing debate about the overall benefit of cholesterol lowering. We performed a novel meta-analysis of all randomized trials of more than 2 years' duration (n = 35 trials) to describe how coronary-heart-disease (CHD), non-CHD, and total mortality are related to cholesterol lowering and to type of intervention. METHODS AND RESULTS: The analytic approach was designed to separate the effects of cholesterol lowering itself from the other effects of the different types of intervention used. For every 10 percentage points of cholesterol lowering, CHD mortality was reduced by 13% (P <.002) and total mortality by 10% (P <.03). Cholesterol lowering had no effect on non-CHD mortality. Certain types of intervention had specific effects independent of cholesterol lowering. Fibrates (clofibrates, 7 trials; gemfibrozil, 2 trials) increased non-CHD mortality by about 30% (P <.01) and total mortality by about 17% (P <.02). Hormones (estrogen, 2 trials; dextrothyroxin, 2 trials) increased CHD mortality in men by about 27% (P <.04), non-CHD mortality by about 55% (P <.03), and total mortality by about 33% (P <.01). No specific effects independent of cholesterol lowering were found due to diet (n = 11) or other interventions (resins, 5; niacin, 3; statins, 2; partial ileal bypass, 1). CONCLUSIONS: The results suggest that cholesterol lowering itself is beneficial but that specific adverse effects of fibrates and hormones increase the risk of CHD (hormones only), non-CHD, and total mortality.

Cholesterol reduction yields clinical benefit: impact of statin trials
Gould, A. L., J. E. Rossouw, et al. (1998), Circulation 97(10): 946-52.
Abstract: BACKGROUND: We determined the effect of incorporating the results of eight recently published trials of Hmg CoA reductase inhibitors ("statins") on the conclusions from our previously published meta-analysis regarding the clinical benefit of cholesterol lowering. METHODS AND RESULTS: We used the same analytic approach as in our previous investigation, separating the specific effects of cholesterol lowering from the effects attributable to the different types of intervention studied. The reductions in coronary heart disease (CHD) and total mortality risk observed for the statins fell near the predictions from our earlier meta-analysis. Including the statin trial findings into the calculations led to a prediction that for every 10 percentage points of cholesterol lowering, CHD mortality risk would be reduced by 15% (P<.001), and total mortality risk would be reduced by 11% (P<.001), as opposed to the values of 13% and 10%, respectively, reported previously. Cholesterol lowering in general and by the statins in particular does not increase non-CHD mortality risk. CONCLUSIONS: Adding the results from the statin trials confirmed our original conclusion that lowering cholesterol is clinically beneficial. The relationships (slope) between cholesterol lowering and reduction in CHD and total mortality risk became stronger, and the standard error of the estimated slopes decreased by about half. Use of statins does not increase non-CHD mortality risk. The effect of the statins on CHD and total mortality risk can be explained by their lipid-lowering ability and appears to be directly proportional to the degree to which they lower lipids.

Cholesterol reduction: ischemic heart disease and mortality from non-ischemic heart diseases
Hansen, P. S. (1994), Ugeskr Laeger 156(17): 2608-9.

Cholesterol reduction: weighing the benefits and risks
Gaziano, J. M., P. R. Hebert, et al. (1996), Ann Intern Med 124(10): 914-8.
Abstract: The National Cholesterol Education Program recommends reducing total and low-density lipoprotein cholesterol levels to decrease the risk for coronary heart disease. The available evidence clearly indicates that higher cholesterol levels increase the risk for coronary heart disease and that cholesterol reduction results in corresponding decreases in risk. In contrast, existing data do not strongly support the idea that cholesterol reduction causes increases in any specific nonvascular cause of death. The outcomes of ongoing, large-scale trials will enable existing guidelines to be refined. However, current recommendations, which encourage nonpharmacologic interventions for about 30% of U.S. adults and cholesterol-reducing drugs for about 7% of U.S. adults, seem both justified and warranted.

Cholesterol redux
Rifkind, B. M. and L. D. Grouse (1990), Jama 264(23): 3060-1.

Cholesterol regulates ABCD2 expression: implications for the therapy of X-linked adrenoleukodystrophy
Weinhofer, I., S. Forss-Petter, et al. (2002), Hum Mol Genet 11(22): 2701-8.
Abstract: X-linked adrenoleukodystrophy (X-ALD) is a severe neurodegenerative disorder with impaired very long-chain fatty acid (VLCFA) metabolism. The disease-associated ABCD1 (ALD) gene encodes a peroxisomal membrane protein, which belongs to the superfamily of ATP-binding cassette transporters. Several treatment regimes have been tried without satisfactory clinical benefit. Recently, the cholesterol-lowering drug lovastatin was reported to normalize VLCFA levels in two out of three clinical studies. This investigation aimed to disclose the molecular mechanism of successful reduction of VLCFA accumulation in order to fill in the gap in the understanding how dietary cholesterol lowering affects the levels of VLCFA in patients with X-ALD and to allow more efficacious treatment. Overexpression of ABCD2 (ALDR), the closest relative of ABCD1, restores VLCFA accumulation in cultured ABCD1-deficient cells. Here we show by real-time PCR that the ABCD2 gene is induced in cultured human fibroblasts and monocytes upon sterol depletion via a mechanism requiring the activation of sterol regulatory element-binding proteins (SREBPs), a family of transcription factors that control the metabolism of cholesterol and fatty acids. This is unexpected and the first report that extends the mechanism of transcriptional regulation by SREBPs to a peroxisomal protein, thus providing a closer link between peroxisomes, cholesterol and fatty acid biosynthesis. Using reporter gene studies, site-directed mutagenesis and gel shift assays, we identified a functional sterol regulatory element in the proximal promoter region of ABCD2. Finally, we demonstrated that ABCD2 induction by sterol depletion significantly reduced the accumulation of VLCFA in X-ALD fibroblasts. Thus, lowering cholesterol leads to SREBP maturation, increased ABCD2 expression and reduced VLCFA accumulation.

Cholesterol regulates ABCD2 gene expression: implications for X-linked adrenoleukodstrophy
Weinhofer, I., S. Forss-Petter, et al. (2003), Adv Exp Med Biol 544: 331-2.

Cholesterol regulates membrane binding and aggregation by annexin 2 at submicromolar Ca(2+) concentration
Ayala-Sanmartin, J., J. P. Henry, et al. (2001), Biochim Biophys Acta 1510(1-2): 18-28.
Abstract: Annexin 2 is a member of the annexin family which has been implicated in calcium-regulated exocytosis. This contention is largely based on Ca(2+)-dependent binding of the protein to anionic phospholipids. However, annexin 2 was shown to be associated with chromaffin granules in the presence of EGTA. A fraction of this bound annexin 2 was released by methyl-beta-cyclodextrin, a reagent which depletes cholesterol from membranes. Restoration of the cholesterol content of chromaffin granule membranes with cholesterol/methyl-beta-cyclodextrin complexes restored the Ca(2+)-independent binding of annexin 2. The binding of both, monomeric and tetrameric forms of annexin 2 was also tested on liposomes of different composition. In the absence of Ca(2+), annexin 2, especially in its tetrameric form, bound to liposomes containing phosphatidylserine, and the addition of cholesterol to these liposomes increased the binding. Consistent with this observation, liposomes containing phosphatidylserine and cholesterol were aggregated by the tetrameric form of annexin 2 at submicromolar Ca(2+) concentrations. These results indicate that the lipid composition of membranes, and especially their cholesterol content, is important in the control of the subcellular localization of annexin 2 in resting cells, at low Ca(2+) concentration. Annexin 2 might be associated with membrane domains enriched in phosphatidylserine and cholesterol.

Cholesterol regulates oxysterol binding protein (OSBP) phosphorylation and Golgi localization in Chinese hamster ovary cells: correlation with stimulation of sphingomyelin synthesis by 25-hydroxycholesterol
Storey, M. K., D. M. Byers, et al. (1998), Biochem J 336 (Pt 1): 247-56.
Abstract: Sphingomyelin (SM) and cholesterol content is positively correlated in cellular membranes, and in several pathological and experimental conditions there is evidence for coregulation. The potential role of oxysterols and oxysterol binding protein (OSBP) in mediating the coregulation of cholesterol and SM was examined using Chinese hamster ovary (CHO) and cholesterol auxotrophic, sterol regulatory defective (SRD) 6 cells. SRD 6 cells grown in the presence or absence of cholesterol for 24 h displayed a 30-50% reduction in SM synthesis compared with control CHO 7 cells. SM synthesis in CHO 7 and cholesterol-supplemented SRD 6 cells was stimulated 2-fold by 25-hydroxycholesterol, but cholesterol-starved SRD 6 cells were unresponsive. Basal and 25-hydroxycholesterol-stimulated SM synthesis was also inhibited in lovastatin-treated wild-type CHO-K1 cells. Lack of 25-hydroxycholesterol activation of SM synthesis in cholesterol-starved SRD 6 and lovastatin-treated CHO-K1 cells was correlated with dephosphorylation of OSBP. In SRD 6 cells, this was evident after 12 h of cholesterol depletion, it occurred equally at all phosphorylation sites and was exacerbated by 25-hydroxycholesterol. Unlike CHO 7 cells, where OSBP was observed in small vesicles and the cytoplasm, OSBP in cholesterol-starved SRD 6 cells was constitutively localized in the Golgi apparatus. Supplementation with non-lipoprotein cholesterol promoted redistribution to vesicles and the cytoplasm. Similarly, OSBP in CHO-K1 cells grown in delipidated serum was predominantly in the Golgi apparatus. Low-density lipoprotein (LDL) supplementation of CHO-K1 cells caused the redistribution of OSBP to the cytoplasm and small vesicles, and this effect was blocked by pharmacological agents inverted question mark3-beta-2-(diethylamino)ethoxyandrost-5-en-17-one and progesterone inverted question mark, which inhibited LDL cholesterol efflux from lysosomes. The results showed that localization of OSBP between the Golgi apparatus and a cytoplasmic/vesicular compartment was responsive to changes in cholesterol content and trafficking. In cholesterol depleted SRD 6 cells, this was accompanied by dephosphorylation of OSBP and attenuation of 25-hydroxycholesterol activation of SM synthesis.

Cholesterol regulates the cell surface expression of glycophospholipid-anchored CD14 antigen on human monocytes
Esfahani, M., R. D. Bigler, et al. (1993), Biochim Biophys Acta 1149(2): 217-23.
Abstract: The CD14 antigen which is expressed on human monocytes and macrophages is a phosphatidylinositol-linked surface protein. We investigated the effects of cellular cholesterol depletion and repletion on cell surface expression of this glycoprotein. Adherent normal human monocytes were cultured for four days in media containing delipidated fetal calf serum which depleted cellular cholesterol. Immunofluorescence analysis demonstrated a markedly diminished surface expression of CD14 on cells cultured in delipidated serum compared to normal serum. Expression of CD64 (high-affinity Fc receptors, Fc gamma RI) also was reduced under these conditions. This inhibition of CD14 expression was overcome by addition to the culture medium of cholesterol, low density lipoprotein, or very low density lipoprotein. All of these supplements replenished cellular cholesterol. Expression of CD64(Fc gamma RI) was not restored by addition of cholesterol. These observations indicate that cholesterol can regulate the surface expression of some phosphatidylinositol-anchored glycoproteins.

Cholesterol regulation of genes involved in sterol trafficking in human THP-1 macrophages
Llaverias, G., D. Lacasa, et al. (2005), Mol Cell Biochem 273(1-2): 185-91.
Abstract: Modulation of the expression of genes involved in the control of cholesterol homeostasis by sterols in macrophages is crucial to foam cell formation. To characterize this regulation in THP-1 macrophages, we examined the effect of sterol loading and unloading on the expression of a number of genes that participate in lipoprotein uptake and cholesterol efflux. Sterol loading by exposure to acetylated LDL for 24 h resulted in an increase in free and esterified cholesterol of 1.4 and 1.8-fold, respectively. Under these conditions, the mRNA levels for SR-A were reduced a 59%, while those of CYP27 were increased by 4.6-fold. However, the expression of other genes involved in cholesterol efflux (ABCA1, ABCG1 and CLA-1) was not modified, despite a high intracellular cholesterol accumulation specially in the form of esterified cholesterol. On the other hand, HDL exposure reduced intracellular cholesterol content to 70%, and caused an increase in the expression of CD36 (78%), SR-A (51%) and CLA-1 (136%). Conversely, the expression of ABCA1, ABCG1 and CYP27 was decreased by 49, 67 and 57%, respectively. These findings indicate that in THP-1 macrophages, the expression of genes for receptors involved in lipoprotein binding and uptake tends to decrease upon cholesterol loading and to increase by cholesterol depletion, while the opposite pattern is found regarding the mRNA levels for proteins involved in cholesterol efflux.

Cholesterol relieves the inhibitory effect of sphingomyelin on type II secretory phospholipase A2
Koumanov, K. S., P. J. Quinn, et al. (1998), Biochem J 336 (Pt 3): 625-30.
Abstract: Secretory type II phospholipase A2 (sPLA2) is inhibited by sphingomyelin (SPH); cholesterol either mixed with the model glycerophospholipid substrate or added to the assay medium as separated liposomes counteracts this inhibition efficiently. The inhibition of fatty acid release assayed by quantitative gas chromatography-MS is observed when SPH is added to erythrocyte membranes as the substrate instead of a readily hydrolysable phosphatidylethanolamine/phosphatidylserine model mixture. Hydrolysis of SPH by Staphylococcus aureus sphingomyelinase suppresses its inhibitory potency. The addition of cholesterol to SPH liposomes with a 1:1 stoichiometry relieves completely the inhibition of sPLA2 exerted by SPH. The mechanism of inhibition suggested by the binding assay is that sPLA2 binds with affinity to the SPH interface, after either phase segregation at the assay temperature or on the pure SPH liposomes added to the incubation medium. Cholesterol is shown to suppress the binding affinity of the enzyme for the SPH interface. A model for inhibition is suggested in which binding of the sphingosine moiety is competitive for sPLA2 (inhibition) or for cholesterol (release of the enzyme).

Cholesterol removal by methyl-beta-cyclodextrin inhibits poliovirus entry
Danthi, P. and M. Chow (2004), J Virol 78(1): 33-41.
Abstract: Upon binding to the poliovirus receptor (PVR), the poliovirus 160S particles undergo a conformational transition to generate 135S particles, which are believed to be intermediates in the virus entry process. The 135S particles interact with host cell membranes through exposure of the N termini of VP1 and the myristylated VP4 protein, and successful cytoplasmic delivery of the genomic RNA requires the interaction of these domains with cellular membranes whose identity is unknown. Because detergent-insoluble microdomains (DIMs) in the plasma membrane have been shown to be important in the entry of other picornaviruses, it was of interest to determine if poliovirus similarly required DIMs during virus entry. We show here that methyl-beta-cyclodextrin (MbetaCD), which disrupts DIMs by depleting cells of cholesterol, inhibits virus infection and that this inhibition was partially reversed by partially restoring cholesterol levels in cells, suggesting that MbetaCD inhibition of virus infection was mediated by removal of cellular cholesterol. However, fractionation of cellular membranes into DIMs and detergent-soluble membrane fractions showed that both PVR and poliovirus capsid proteins localize not to DIMs but to detergent-soluble membrane fractions during entry into the cells, and their localization was unaffected by treatment with MbetaCD. We further demonstrate that treatment with MbetaCD inhibits RNA delivery after formation of the 135S particles. These data indicate that the cholesterol status of the cell is important during the process of genome delivery and that these entry pathways are distinct from those requiring DIM integrity.

Cholesterol Articles and Abstracts

Cholesterol Journal Articles