Hyperlipidemias: Huang Y

Mahley RW, Huang Y, Rall SC. · Gladstone Institute of Cardiovascular Disease, University of California, San Francisco, CA 94141-9100, USA. · J Lipid Res. · Pubmed #10552997 links to  free full text

Abstract: Type III hyperlipoproteinemia (HLP) is a genetic disorder characterized by accumulation of remnant lipoproteins in the plasma and development of premature atherosclerosis. Although receptor binding-defective forms of apolipoprotein (apo) E are the common denominator in this disorder, a number of apparent paradoxes concerning its pathogenesis still exist. However, studies in transgenic animals are resolving the mechanisms underlying this disorder. PARADOX I: Defective apoE (commonly apoE2) is essential but not sufficient to cause overt type III HLP. In fact, most apoE2 homozygotes are hypolipidemic. Studies in apoE2 transgenic models have demonstrated the impact of other genes or hormones in converting the hypolipidemia to hyperlipidemia. PARADOX II: Among apoE2 homozygotes, men are more susceptible than women to type III HLP. Transgenic studies have shown that estrogen affects both LDL receptor expression and lipolytic processing, explaining the resistance of women to this disorder until after menopause. PARADOX III: ApoE deficiency is associated with hypercholesterolemia, whereas the type III HLP phenotype is characterized by both hypercholesterolemia and hypertriglyceridemia. The hypercholesterolemia is caused by impaired receptor-mediated clearance, whereas the hypertriglyceridemia is caused primarily by impaired lipolytic processing of remnants and increased VLDL production associated with increased levels of apoE. PARADOX IV: ApoE2 is associated with recessive inheritance of this disorder, whereas other defective apoE variants are associated with dominant inheritance. Determinants of the mode of inheritance are the differential binding of apoE variants to the LDL receptor versus the HSPG/LRP complex and the preference of certain apoE variants for specific lipoproteins. Thus, the pathogenesis of this sometimes mysterious disorder has been clarified.

Li JJ, Li YS, Chu JM, Zhang CY, Wang Y, Huang Y, Chen J, Yuan JQ, Huang YL. · Department of Cardiology, Fu Wai Hospital, Chinese Academy of Medical Science, Peking Union Medical College, Beilishi Road 167, Beijing 100037, People's Republic of China. · Clin Chim Acta. · Pubmed #16343471 No free full text.

Abstract: BACKGROUND: Atherosclerosis has been considered to be an inflammatory process. In addition to its lipid-lowering properties, statin has been shown to decrease the concentrations of inflammatory markers resulting in reduction of cardiovascular events. Emerging data suggest that withdrawal of statin might be associated with increased cardiac events. The mechanism for this phenomenon, however, is still unclear. We investigated whether acute termination of statin treatment could result in rebound of inflammatory markers, such as C-reactive protein (CRP) and interleukin-6 (IL-6), in patients with hyperlipidemia. METHODS: Seventeen patients (11 men and 6 women, mean age 51+/-7 years) with hyperlipidemia were given 40 mg/day of pravastatin for 6 weeks. The concentrations of plasma CRP and IL-6 were evaluated before receiving the statin therapy, immediately after 6 weeks of pravastatin therapy, and at days 1, 3 and 7 after withdrawal of pravastatin therapy. The lipid profile was also evaluated at baseline, 6 weeks of therapy, and at day 7 after terminating pravastatin. RESULTS: Pravastatin therapy induced significant reductions in total cholesterol (TC, 6.88+/-0.36 vs. 5.27+/-0.23 mmol/l, p<0.01), low-density lipoprotein (LDL) cholesterol (4.28+/-0.25 vs. 3.06+/-0.14 mmol/l, p<0.01), CRP (0.28+/-0.16 vs. 0.20+/-0.08 mg/l, p<0.01), and IL-6 (8.4+/-0.6 vs. 6.7+/-0.4 pg/dl, p<0.01). Although the TC and LDL-cholesterol did not change during the 7-day period after withdrawal of pravastatin therapy, the concentrations of CRP and IL-6 increased at day 3 (CRP: 0.20+/-0.08 vs. 0.27+/-0.12 mg/l, and IL-6: 6.7+/-0.4 vs. 7.7+/-0.6 pg/dl, p<0.05 respectively) and at day 7 (CRP: 0.20+/-0.08 vs. 0.30+/-0.14 mg/l, and IL-6: 6.7+/-0.4 vs. 8.7+/-0.8 pg/dl, p<0.01 respectively) after withdrawal of pravastatin therapy. No correlation between increase of CRP as well as IL-6 and small changes of LDL-cholesterol concentrations was found after withdrawal of pravastatin therapy at day 7 (r=-0.021 and r=-0.044 respectively, p>0.05 respectively). CONCLUSIONS: 6 weeks after pravastatin therapy could significant modify the lipid profile and decrease the inflammatory markers including CRP and IL-6 in patients with hyperlididemia. Moreover, statin therapy discontinuation could induce a rebound phenomenon of inflammatory response representing an increase in some inflammatory markers, which is independent of changes of lipid parameters.

Wang Z, Huang Y, Zou J, Cao K, Xu Y, Wu JM. · Department of cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjiang 210029, China. · Int J Mol Med. · Pubmed #11745001 No free full text.

Abstract: Low to moderate consumption of red wine reportedly has a relatively greater benefit than other alcoholic beverages in the prevention of atherosclerosis and coronary heart disease (CHD). This beneficial effect is increasingly attributed to the polyphenol resveratrol, present in red wine. In the present study, we investigated the effects of resveratrol and red wine on aggregation of platelets isolated from healthy, normotensive male volunteers and in rabbits with experimental hypercholesterolemia. Platelet aggregation rate (PAR) was measured using Born's method. The results showed that aggregation of platelets from healthy subjects induced in vitro by collagen (5 microg/ml), thrombin (0.33 units/ml), and ADP (4 microM) was significantly inhibited by 10-1000 microM resveratrol, in a concentration-dependent manner. Hypercholesterolemic rabbits showed enhanced ADP-induced platelet aggregation; the average PAR increased from 39.5+/-5.9% in normal animals to 61.0+/-7.0% in the high-cholesterol fed group (n=8, p<0.001). Resveratrol (4 mg/kg/day) inhibited ADP-induced platelet aggregation in vivo by maintaining the PAR at 35.7+/-6.3% (vs. 39.5+/-5.9% for control rabbits, n=8, p=0.228), but had no effect on serum lipid levels. Similarly platelet aggregation in hypercholesterolemic rabbits was also inhibited when animals received intragastrically Chinese red wine (with or without alcohol, 4 ml/kg/day). These results suggest that resveratrol can inhibit platelet aggregation both in vitro and in vivo, which conceivably could be one of the mechanisms by which this red wine polyphenol exerts its cardioprotective effects.

Li Q, Fan P, Bai H, Liu R, Huang Y, Wang X, Wu H, Liu Y, Liu B. · Unit of Laboratory Medicine, West China Second Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China. · Clin Chim Acta. · Pubmed #19239905 No free full text.

Abstract: BACKGROUND: ApoL-I is a newly found component of HDL, and has a potential role in the lipid metabolism. This study was mainly to examine the possible association of the ApoL-I gene polymorphism with endogenous hypertriglyceridemia (HTG) in Chinese population. METHODS: Three hundred and thirty five Han Chinese (102 HTG and 233 healthy control subjects) in Chengdu area were studied using PCR-RFLP analysis. RESULTS: The Lys and Glu allele frequencies of apoL-I gene at Lys166Glu site in HTG and normal control groups were 0.857, 0.143 and 0.801, 0.199, respectively; The Ile and Met allele frequencies of the gene at Ile244Met site in HTG and the control groups were 0.868, 0.132 and 0.812, 0.188 respectively. The 166Glu and 244Met allele frequencies of the 2 polymorphisms in HTG subjects were not different from those in the normal controls, respectively (P>0.05). In HTG group, subjects with genotype Lys/lys of Lys166Glu site had a higher serum mean concentration of TG as compared to those of Glu allele carriers (3.64+/-1.55 mmol/l vs 2.86+/-0.51 mmol/l, P<0.05). Subjects with genotype Ile/Ile of Ile244Met site had a higher serum mean concentration of TG as compared to those of Met allele carriers (3.59+/-1.56 mmol/l vs 2.94+/-0.88 mmol/l, P<0.05). CONCLUSIONS: The Lys166Glu and Ile244Met polymorphisms in apoL-I gene are associated with TG levels in subjects with endogenous hypertriglyceridemia in Chinese. However, these polymorphisms were not associated with the risk of HTG in the population.

Huang Y, Bai H, Fan P, Liu R, Liu Y, Liu BW. · West China Second Hospital, Sichuan University, Chengdu, Sichuan, 610041 People's Republic of China. · Zhonghua Yi Xue Yi Chuan Xue Za Zhi. · Pubmed #18683147 No free full text.

Abstract: OBJECTIVE: To investigate the effects of the -384A>C polymorphism in the promoter region of endothelial lipase (EL) gene on serum lipid and apolipoprotein levels in healthy normolipidemic (HTG) and endogenous hypertriglyceridemic (HTG) subjects. METHODS: Two hundred and fourteen healthy normolipidemic and 103 endogenous hypertriglyceridemic subjects from a population of Chinese Han nationality in Chengdu area were studied using restriction fragment length polymorphism (RFLPs). Serum lipids were measured by enzymatic kits and apolipoproteins AI, AII, B100, CII, CIII and E were measured by the radial immunadiffussion kits. RESULTS: The frequency of the C allele at the -384A>C site in EL gene in the population (0.178) was higher than that of Japanese population (0.119) and Japanese Americans (0.115) (P < 0.01 and P < 0.01), respectively. No significant difference between normolipidemic and HTG groups was found in both allele and genotype frequencies. In normal group, subjects of the C allele carriers (A/C and C/C genotype carriers) had a higher serum mean concentration of TC, LDL-C and nHDL-C when compared with those of genotype AA (5.23 +/- 0.74 mmol/L vs 4.93 +/- 0.74 mmol/L, P=0.025; 3.27 +/- 0.74 mmol/L vs 2.98 +/- 0.80 mmol/L, P=0.038; 3.81 +/- 0.73 mmol/L vs 3.49 +/- 0.85 mmol/L, P=0.031, respectively). Similar result was only observed in female subgroup when male and female subgroups were further separated. No significant changes of lipid and lipoprotein levels were observed in the polymorphism in HTG group. CONCLUSION: These results suggest that the -384A>C polymorphism in the promoter region of the endothelial lipase gene is associated with serum TC, LDL-C, and nHDL-C levels in healthy Chinese subjects in Chengdu area, but not associated with the lipid levels in the endogenous hypertriglyceridmic group.

Ng CH, Qiang Yao X, Huang Y, Chen ZY. · Food and Nutritional Sciences Programme, Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China. · Br J Nutr. · Pubmed #17916278 No free full text.

Abstract: The present study was to test the relative hypercholesterolaemic and atherogenic potency of oxidised cholesterol (OxC) and non-oxidised cholesterol in hamsters. An OxC mixture, prepared by heating pure cholesterol (100 g) at 160 degrees C in air for 72 h, contained 78 % cholesterol and 22 % OxC. Fifty Golden Syrian hamsters were randomly divided into five groups of ten animals and fed the control diet, a 0.05 % cholesterol diet (C-0.05), a 0.10 % cholesterol diet (C-0.1), a 0.05 % OxC mixture diet (OxC-0.05) or a 0.10 % OxC mixture diet (OxC-0.1), respectively. The OxC-0.05 and OxC-0.1 groups were more hypercholesterolaemic and had serum total cholesterol 22 and 12 % higher than the corresponding C-0.05 and C-0.1 hamsters (P < 0.05). The OxC-0.1 group demonstrated greater deposition of cholesterol and had a larger area of atherosclerotic plaque in the aorta than the corresponding C-0.1 hamsters (P < 0.05). Similarly, the aorta in the OxC-0.1 group showed greater inhibition on acetylcholine-induced relaxation compared with that in the C-0.1 hamsters. It was concluded that OxC was much more hypercholesterolaemic and atherogenic than cholesterol.

Wang Z, Zou J, Cao K, Hsieh TC, Huang Y, Wu JM. · Department of Cardiology, The First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, PR China. · Int J Mol Med. · Pubmed #16142383 No free full text.

Abstract: Moderate consumption of red wine is associated with a reduced risk of coronary heart disease (CHD). This phenomenon is based on data from epidemiological observations known as the French paradox, and has been attributed to CHD-protective phytochemicals, e.g. resveratrol in red wine. Since red wine also contains alcohol, it is conceivable that alcohol interacts with resveratrol to elicit the observed cardioprotective effects. To determine whether resveratrol has alcohol-independent affects, we compared cardioprotective properties of dealcoholized Chinese red wine with alcohol-containing Chinese red wine having comparable amounts of resveratrol, using a hypercholesterolemic rabbit model and resveratrol as a reference. Animals fed a high cholesterol (1.5%) diet were simultaneously given water containing resveratrol (3 mg/kg/day) or red wine (4 ml/kg/day) containing 3.98 mg/l and 3.23 mg/l resveratrol for regular and dealcoholized red wine, respectively, for a 12-week duration. Total, HDL- and LDL-cholesterol and triglyceride levels in the plasma were measured before and after the cholesterol challenge. Atherosclerotic plaques in the thoracic aorta were evaluated using histochemical methods. Vascular and endothelial functions in the femoral artery were also assessed by ultrasonographic image analysis. High cholesterol-fed animals showed a significant increase in plasma levels of total, HDL- and LDL-cholesterol, but not triglycerides, compared to those fed a regular diet. Dietary cholesterol-elicited lipid changes were similarly observed in animals concurrently fed dealcoholized red wine, red wine or resveratrol. In contrast, whereas atherosclerotic lesions were clearly evident in specimens prepared from the thoracic aorta of high cholesterol-fed animals, the size, density, and mean area of atherosclerotic plaques, and thickness of the intima layer were significantly reduced in rabbits given dealcoholized red wine, red wine, or resveratrol. These results were in agreement with data obtained by an ultrasound analysis of endothelial function, which showed a 25% reduction in flow-mediated dilation (FMD) in rabbits fed a high cholesterol diet compared to animals on control diet. This decrease was effectively prevented by the simultaneous exposure to dealcoholized red wine, red wine, or resveratrol. Our study shows that animals given dealcoholized red wine exhibited cardio-active effects comparable to those of animals orally administered resveratrol, and suggests that wine polyphenolics, rather than alcohol present in red wine, suffice in exerting cardioprotective properties. The results also provide support for the notion that resveratrol and phytochemicals in red wine can suppress atherosclerosis without affecting plasma lipid levels.

Hodoğlugil U, Williamson DW, Huang Y, Mahley RW. · Gladstone Institute of Cardiovascular Disease, 1650 Owens Street, San Francisco, CA 94158, USA. · Atherosclerosis. · Pubmed #15935359 No free full text.

Abstract: The role of high levels of high density lipoprotein cholesterol (HDL-C) in protection against development of atherosclerosis is generally attributed to its role in reverse cholesterol transport, and the ATP binding cassette transporter A1 (ABCA1) is a key element of this process. We examined polymorphisms in ABCA1 in Turks, a population characterized by very low HDL-C levels. We discovered 36 variations in ABCA1 and genotyped informative polymorphisms in over 2,300 subjects. The rare alleles of C-14T and V771M polymorphisms were associated with higher HDL-C levels in men and, in combination with the rare alleles of R219K and I883M, respectively, with higher HDL-C in both sexes. Rare alleles of the C-14T and V771M polymorphisms were more frequent in the high HDL-C (>OR=40mg/dl) than in the low HDL-C group (<OR=30mg/dl) in men (P<0.05). Moreover, the T allele of C-14T had more in vitro transcriptional activity than the C allele (20-88%), depending on the cell line (P<0.05), suggesting its functionality. Haplotype construction and haplotype association with phenotype were performed in the promoter and coding region of ABCA1 separately. Analysis of the promoter haplotype block supported the association with the C-14T polymorphism. The C-14T and R219K polymorphisms were on different haplotype blocks. Analysis of the coding region structure revealed that the rare M allele of V771M was distributed predominantly among three common haplotypes, but the sum of their frequencies comprise only two-thirds of the frequency of the M allele. The rare alleles of the V771M and the I883M polymorphisms do not exist together on any of the common haplotypes. In conclusion, we describe a functional promoter polymorphism (C-14T) and a coding sequence variant (V771M) of ABCA1 and their interactions with two other variants (R219K and I883M) on plasma HDL-C levels in Turks.

Huang Y, Walker KE, Hanley F, Narula J, Houser SR, Tulenko TN. · Department of Surgery, Thomas Jefferson University College of Medicine, Philadelphia, Pa 19107, USA. · Circulation. · Pubmed #14676147 links to  free full text

Abstract: BACKGROUND: Although hypercholesterolemia is a well-established risk factor for coronary artery disease, little is known regarding its direct effects on cardiac function. METHODS AND RESULTS: We examined the effects of cholesterol feeding (0.5%) on cardiac function in rabbits. After 10 weeks, both systolic shortening and diastolic relaxation rates were impaired without any change in aortic pressure or ventricular hypertrophy. However, sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA)-2 mRNA levels were reduced within 4 days after initiation of cholesterol feeding. After this effect, SERCA-2 protein and SERCA-mediated Ca uptake into sarcoplasmic reticulum vesicles were impaired, and the ratio of MHC-beta to MHC-alpha mRNA increased 5-fold. Suppression of the SERCA-2 message correlated temporally with enrichment of the cardiac sarcolemma with cholesterol. CONCLUSIONS: These data demonstrate that dietary hypercholesterolemia induces a "cholesterol cardiomyopathy" characterized by systolic and diastolic dysfunction. These alterations were independent of vascular disease and demonstrate a dietary link to cardiac dysfunction.

Huang Y, Dai G, Feng Z, Lu C, Cheng B, Wang Q, Nie F, Li J. · Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. · Chin Med J (Engl). · Pubmed #14642156 links to  free full text

Abstract: OBJECTIVE: To investigate the effect of micronized fenofibrate on vascular endothelial function in patients with hypertriglyceridemia. METHODS: Using high-resolution ultrasound, we measured flow- and nitroglycerin-induced dilatation of the brachial artery in 30 patients with hypertriglyceridemia before and after treatment with micronized fenofibrate at a dose of 200 mg once daily for 4 weeks. Simultaneously, both serum lipid and plasma endothelin (ET) levels were determined. RESULTS: After micronized fenofibrate therapy, serum triglyceride (TG) levels decreased significantly (P < 0.05). Plasma ET levels also decreased markedly [(82.66 +/- 15.46) microg/L vs. (106.22 +/- 19.16) microg/L, P < 0.001]. Flow-induced vasodilatation was much improved (11.0% +/- 9.0% vs 2.7% +/- 2.0%, P < 0.01). However, no significant changes in vasodilatation occurred in response to nitroglycerin (16.2% +/- 6.0% vs 15.0% +/- 5.0%, P > 0.05) in patients with hypertriglyceridemia. CONCLUSIONS: Micronized fenofibrate can improve impaired endothelium-dependent vasodilatation in patients with hypertriglyceridemia. Improving endothelial function may also be the mechanism responsible for the beneficial effects of micronized fenofibrate.

Schneider MP, Hilgers KF, Huang Y, Delles C, John S, Oehmer S, Schmieder RE. · Universität Erlangen-Nürnberg, Medizinische Klinik IV/4, Klinikum Nürnberg Süd, Breslauer Strasse 201, D-90471 Nuremberg, Germany. · Clin Sci (Lond). · Pubmed #12639216 No free full text.

Abstract: Oxidative stress plays a major pathogenetic role in cardiovascular disease. The C242T variant of the CYBA gene encoding the p22phox subunit of the NAD(P)H oxidase, a major source of superoxide production, has been shown to be associated with coronary artery disease and with vascular superoxide production in human veins ex vivo. Since superoxide degrades nitric oxide (NO), we hypothesized that the C242T variant influences endothelium-dependent vasodilation of the human forearm vasculature in vivo. In the present study, 90 subjects with elevated cholesterol levels were stratified for the C242T polymorphism of the CYBA p22phox gene. Endothelium-dependent and -independent vasodilation were assessed by plethysmographic monitoring of forearm blood flow responses to intra-arterial infusion of acetylcholine and sodium nitroprusside respectively. N(G)-Monomethyl-L-arginine (L-NMMA) was infused to analyse NO-mediated basal vascular tone. Baseline parameters (age, gender, blood pressure, body mass index, cholesterol level) were similar across the genotypes. No differences in forearm blood flow responses to the intra-arterial infusion of acetylcholine, sodium nitroprusside or L-NMMA were found across the CYBA p22phox genotypes. Our sample size of n =90 had a power of >80% (beta=0.20) with a P value of <0.05 (alpha=0.05) to detect a difference greater than 156% in the forearm blood flow response to acetylcholine across genotypes (S.D. 336%; average increase in forearm blood flow=514%). In conclusion, at a power of 80%, our study excludes a major effect of the C242T CYBA p22phox polymorphism on acetylcholine-mediated endothelium-dependent vasodilation and basal NO-mediated vascular tone of the human forearm circulation in subjects with hypercholesterolaemia.

Zhang Z, Ho WK, Huang Y, James AE, Lam LW, Chen ZY. · Department of Biochemistry, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong, The People's Republic of China. · J Nutr. · Pubmed #11773500 links to  free full text

Abstract: The present study examined the hypolipidemic activity of hawthorn fruit. New Zealand white rabbits were fed one of three diets, a reference diet with no cholesterol added (NC), a high cholesterol diet (1 g/100 g, HC) and a HC diet supplemented with 2 g/100 g hawthorn fruit powder (HC-H). After 12 wk, serum total cholesterol (TC) and triacylglycerols (TG) were 23.4 and 22.2% lower, respectively, in the hawthorn fruit group compared with the HC rabbits (P < 0.05). Hawthorn supplementation led to 50.6% less cholesterol accumulation in aorta (P < 0.05) and 23-95% greater excretion of neutral and acidic sterols (P < 0.05). Supplementation of hawthorn fruit did not affect the activities of hepatic 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMG-CoA-R) or cholesterol 7alpha-hydroxylase (CH) but it suppressed the activity of intestinal acyl CoA:cholesterol acyltransferase (ACAT, P < 0.05). The results suggest that the mechanism by which hawthorn fruit decreases serum cholesterol involves, at least in part, the inhibition of cholesterol absorption mediated by down-regulation of intestinal ACAT activity.

Lee Y, Lin RS, Sung FC, Yang C, Chien K, Chen W, Su T, Hsu H, Huang Y. · Department of Internal Medicine, National Taiwan University College of Medicine, 7 Chung-Shan South Road, 100, Taipei, Taiwan. · J Clin Epidemiol. · Pubmed #10942867 No free full text.

Abstract: A cohort consisting of 3602 residents (82.8% of the target population) aged 35 years and older was established in 1990 in the Chin-Shan Community, a suburb 20 miles outside of metropolitan Taipei, Taiwan. The long-term objective was to investigate the prospective impact on cardiovascular health in a society undergoing transition from a developing to a developed nation. This article presents the study design, selected baseline risk factors of cardiovascular diseases (CVD), and CVD events at the 5-year follow-up evaluation with an emphasis on sociodemographic differences. The multivariate logistic regression analyses revealed that white-collar individuals were more likely than blue-collar workers to have dyslipidemia including high-density lipoprotein cholesterol (HDL-C) levels <35 mg/dl [odds ratio (OR) = 1.7, 95% confidence interval (CI) = 1.2-2.4] and low-density lipoprotein cholesterol (LDL-C) levels >/=160 mg/dl (OR = 1.3, 95% CI = 1.0-1.7). However, they were at slightly lower risk for stroke and CVD/sudden death, and at moderately higher risk for coronary artery disease and diabetes, although both these trends were not significant. Men were more likely than women to have HDL-C levels <35 mg/dl (OR = 1.8, 95% CI = 1.4-2.2), but they were less likely to have LDL-C levels >/=160 mg/dl (OR = 0.7, 95% CI = 0.6-0.8). The risk of CVD/sudden death was higher for men than for women during the follow-up period (OR = 1.9, 95% CI = 1.3-2.9). This could be due to risk factors such as a much higher prevalence of tobacco (61.9% vs. 4.5%) and alcohol (43.7% vs. 6.4%) use in men. In conclusion, individuals of higher socioeconomic status have a higher prevalence of dyslipidemia but slightly lower 5-year incidence of CVD events.

Huang Y, Ji ZS, Brecht WJ, Rall SC, Taylor JM, Mahley RW. · Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94141-9100, USA. · Arterioscler Thromb Vasc Biol. · Pubmed #10591675 links to  free full text

Abstract: The differential effects of overexpression of human apolipoprotein (apo) E3 on plasma cholesterol and triglyceride metabolism were investigated in transgenic rabbits expressing low (<10 mg/dL), medium (10 to 20 mg/dL), or high (>20 mg/dL) levels of apoE3. Cholesterol levels increased progressively with increasing levels of apoE3, whereas triglyceride levels were not significantly affected at apoE3 levels up to 20 mg/dL but were markedly increased at levels of apoE3 >20 mg/dL. The medium expressers had marked hypercholesterolemia (up to 3- to 4-fold over nontransgenics), characterized by an increase in low density lipoprotein (LDL) cholesterol, while the low expressers had only slightly increased plasma cholesterol levels. The medium expressers displayed an 18-fold increase in LDL but also had a 2-fold increase in hepatic very low density lipoprotein (VLDL) triglyceride production, an 8-fold increase in VLDL apoB, and a moderate decrease in the ability of the VLDL to be lipolyzed. However, plasma clearance of VLDL was increased, likely because of the increased apoE3 content. The increase in LDL appears to be due to an enhanced competition of VLDL for LDL receptor binding and uptake, resulting in the accumulation of LDL. The combined hyperlipidemia of the apoE3 high expressers (>20 mg/dL) was characterized by a 19-fold increase in LDL cholesterol but also a 4-fold increase in hepatic VLDL triglyceride production associated with a marked elevation of plasma VLDL triglycerides, cholesterol, and apoB100 (4-, 9-, and 25-fold over nontransgenics, respectively). The VLDL from the high expressers was much more enriched in apoE3 and markedly depleted in apoC-II, which contributed to a >60% inhibition of VLDL lipolysis. The combined effects of stimulated VLDL production and impaired VLDL lipolysis accounted for the increases in plasma triglyceride and VLDL concentrations in the apoE3 high expressers. The hyperlipidemic apoE3 rabbits have phenotypes similar to those of familial combined hyperlipidemia, in which VLDL overproduction is a major biochemical feature. Overall, elevated expression of apoE3 appears to determine plasma lipid levels by stimulating hepatic VLDL production, enhancing VLDL clearance, and inhibiting VLDL lipolysis. Thus, the differential expression of apoE may, within a rather narrow range of concentrations, play a critical role in modulating plasma cholesterol and triglyceride levels and may represent an important determinant of specific types of hyperlipoproteinemia.