Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels.

Genetic factors have been shown to play an important role in determining interindividual variation in plasma HDL-C levels, but the specific genetic determinants of HDL cholesterol (HDL-C) levels have not been elucidated. In this study, the effects of variation in the genomic regions encoding hepatic lipase, apolipoprotein AI/CIII/AIV, and the cholesteryl ester transfer protein on plasma HDL-C levels were examined in 73 normotriglyceridemic, Caucasian nuclear families. Genetic factors accounted for 56.5 +/- 13% of the interindividual variation in plasma HDL-C levels. For each candidate gene, adjusted plasma HDL-C levels of sibling pairs who shared zero, one, or two parental alleles identical-by-descent were compared using sibling-pair linkage analysis. Allelic variation in the genes encoding hepatic lipase and apolipoprotein AI/CIII/AIV accounted for 25 and 22%, respectively, of the total interindividual variation in plasma HDL-C levels. In contrast, none of the variation in plasma HDL-C levels could be accounted for by allelic variation in the cholesteryl ester transfer protein. These findings indicate that a major fraction of the genetically determined variation in plasma HDL-C levels is conferred by allelic variation at the hepatic lipase and the apolipoprotein AI/CIII/AIV gene loci.     

Apolipoproteins and coronary artery disease

In this study, we compared the relative utility of plasma levels of cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and apolipoproteins in identifying men with angiographically significant coronary artery disease in a combined sample of consecutive male patients undergoing coronary angiography (N = 304) and healthy, normal male control subjects (N = 135). The plasma apolipoprotein levels were measured by using specific radioimmunoassays. We found that plasma levels of apolipoprotein A-I, followed by those of apolipoproteins A-II and B, were better discriminators than plasma cholesterol, triglycerides, or HDL cholesterol levels for identifying those with coronary artery disease. In confirmation of previous findings, the presence of coronary artery disease resulted in lower levels of apolipoproteins A-I and A-II and HDL cholesterol and higher levels of apolipoprotein B, cholesterol, and triglycerides. Linear and quadratic discriminant function analysis demonstrated that by using the age of the patients and apolipoprotein A-I, A-II, and B levels, one could correctly classify patients either as being normal or as having angiographically significant coronary artery disease in more than 75% of the cases. Thus, plasma apolipoprotein levels (especially A-I and A-II) may be considerably better markers for coronary artery disease than traditional lipid determinations.     

Mechanism of action of gemfibrozil on lipoprotein metabolism.

Gemfibrozil is a potent lipid regulating drug whose major effects are to increase plasma high density lipoproteins (HDL) and to decrease plasma triglycerides (TG) in a wide variety of primary and secondary dyslipoproteinemias. Its mechanism of action is not clear. Six patients with primary familial endogenous hypertriglyceridemia with fasting chylomicronemia (type V lipoprotein phenotype) with concurrent subnormal HDL cholesterol levels (HDL deficiency) were treated initially by diet and once stabilized, were given gemfibrozil (1,200 mg/d). Each patient was admitted to the Clinical Research Center with metabolic kitchen facilities, for investigation of HDL and TG metabolism immediately before and after 8 wk of gemfibrozil treatment. Gemfibrozil significantly increased plasma HDL cholesterol, apolipoprotein (apo) AI, and apo AII by 36%, 29%, and 38% from base line, respectively. Plasma TG decreased by 54%. Kinetics of apo AI and apo AII metabolism were assessed by analysis of the specific radioactivity decay curves after injection of autologous HDL labeled with 125I. Gemfibrozil increased synthetic rates of apo AI and apo AII by 27% and 34%, respectively, without changing the fractional catabolic rates. Stimulation of apo AI and apo AII synthesis by gemfibrozil was associated with the appearance in plasma of smaller (and heavier) HDL particles as assessed by gradient gel electrophoresis and HDL composition. Postheparin extra-hepatic lipoprotein lipase activity increased significantly by 25% after gemfibrozil, and was associated with the appearance in plasma of smaller very low density lipoprotein particles whose apo CIII:CII ratio was decreased. These data suggest that gemfibrozil increases plasma HDL levels by stimulating their synthesis. Increased transport (turnover) of HDL induced by gemfibrozil may be significant in increasing tissue cholesterol removal in these patients.     

Familial apolipoprotein AI and apolipoprotein CIII deficiency. Subclass distribution,composition, and morphology of lipoproteins in a disorder associated with premature atherosclerosis.

Lipoprotein classes isolated from the plasma of two patients with apolipoprotein AI (apo AI) and apolipoprotein CIII (apo CIII) deficiency were characterized and compared with those of healthy, age- and sex-matched controls. The plasma triglyceride values for patients 1 and 2 were 31 and 51 mg/dl, respectively, and their cholesterol values were 130 and 122 mg/dl, respectively; the patients, however, had no measurable high density lipoprotein (HDL)-cholesterol. Analytic ultracentrifugation showed that patients'' S degrees f 0-20 lipoproteins possess a single peak with S degrees f rates of 7.4 and 7.6 for patients 1 and 2, respectively, which is similar to that of the controls. The concentration of low density lipoprotein (LDL) (S degrees f 0-12) particles, although within normal range (331 and 343 mg/dl for patients 1 and 2, respectively), was 35% greater than that of controls. Intermediate density lipoproteins (IDL) and very low density lipoproteins (VLDL) (S degrees f 20-400) were extremely low in the patients. HDL in the patients had a calculated mass of 15.4 and 11.8 mg/dl for patients 1 and 2, respectively. No HDL could be detected by analytic ultracentrifugation, but polyacrylamide gradient gel electrophoresis (gge) revealed that patients possessed two major HDL subclasses: (HDL2b)gge at 11.0 nm and (HDL3b)gge at 7.8 nm. The major peak in the controls, (HDL3a)gge, was lacking in the patients. Gradient gel analysis of LDL indicated that patients'' LDL possessed two peaks: a major one at 27 nm and a minor one at 26 nm. The electron microscopic structure of patients'' lipoprotein fractions was indistinguishable from controls. Patients'' HDL were spherical and contained a cholesteryl ester core, which suggests that lecithin/cholesterol acyltransferase was functional in the absence of apo AI. The effects of postprandial lipemia (100-g fat meal) were studied in patient 1. The major changes were the appearance of a 33-nm particle in the LDL density region of 1.036-1.041 g/ml and the presence of discoidal particles (12% of total particles) in the HDL region. The latter suggests that transformation of discs to spheres may be delayed in the patient. The simultaneous deficiency of apo AI and apo CIII suggests a dual defect in lipoprotein metabolism: one in triglyceride-rich lipoproteins and the other in HDL. The absence of apo CIII may result in accelerated catabolism of triglyceride-rich particles and an increased rate of LDL formation. Additionally, absence of apo CIII would favor rapid uptake of apo E-containing remnants by liver and peripheral cells. Excess cellular cholesterol would not be removed by the reverse cholesterol transport mechanism since HDL levels are exceedingly low and thus premature atherosclerosis occurs.     

Role of lipoprotein lipase in the regulation of high density lipoprotein apolipoprotein metabolism. Studies in normal and lipoprotein lipase-inhibited monkeys.

Mechanisms that might be responsible for the low levels of high density lipoprotein (HDL) associated with hypertriglyceridemia were studied in an animal model. Specific monoclonal antibodies were infused into female cynomolgus monkeys to inhibit lipoprotein lipase (LPL), the rate-limiting enzyme for triglyceride catabolism. LPL inhibition produced marked and sustained hypertriglyceridemia, with plasma triglyceride levels of 633-1240 mg/dl. HDL protein and cholesterol and plasma apolipoprotein (apo) AI levels decreased; HDL triglyceride (TG) levels increased. The fractional catabolic rate of homologous monkey HDL apolipoproteins injected into LPL-inhibited animals (n = 7) was more than double that of normal animals (0.094 +/- 0.010 vs. 0.037 +/- 0.001 pools of HDL protein removed per hour, average +/- SEM). The fractional catabolic rate of low density lipoprotein apolipoprotein did not differ between the two groups of animals. Using HDL apolipoproteins labeled with tyramine-cellobiose, the tissues responsible for this increased HDL apolipoprotein catabolism were explored. A greater proportion of HDL apolipoprotein degradation occurred in the kidneys of hypertriglyceridemic than normal animals; the proportions in liver were the same in normal and LPL-inhibited monkeys. Hypertriglyceridemia due to LPL deficiency is associated with low levels of circulating HDL cholesterol and apo AI. This is due, in part, to increased fractional catabolism of apo AI. Our studies suggest that variations in the rate of LPL-mediated lipolysis of TG-rich lipoproteins may lead to differences in HDL apolipoprotein fractional catabolic rate.     

The Tromsø Heart Study: Serum apolipoprotein Al concentration in relation to future coronary heart disease

The concentrations of apolipoprotein AI, a major peptide of high density lipoprotein (HDL), have been measured by immunoelectrophoresis in samples of serum from twelve subjects who subsequently developed a coronary event during 2 years of follow-up and compared with those in serum from sixteen matched control subjects. The mean apolipoprotein AI concentration in the cases was significantly lower than that in the controls, independently of the serum total cholesterol and triglyceride concentrations. There was no significant difference between the cases and controls in mean HDL cholesterol: apolipoprotein AI ratio. Within several case-control pairs, however, the difference in apolipoprotein AI concentration was proportionately much less than that in HDL cholesterol. On discriminant function analysis, apolipoprotein AI concentration was a less powerful predictor of coronary heart disease than was HDL cholesterol.     

DNA polymorphisms of apolipoprotein B and AI/CIII genes and response to gemfibrozil treatment.

Apolipoprotein B XbaI polymorphism and apolipoprotein AI/CIII SstI polymorphism have been found to be associated with variations in serum lipoprotein levels. We investigated whether these gene polymorphisms are involved in determining the lipid-modulating action of gemfibrozil. Of the 221 male subjects with hyperlipidemia studied, 121 responded well to the treatment with more than a 25% reduction in the non-high-density lipoprotein cholesterol level, whereas 100 were nonresponders. Among responders, but not nonresponders, homozygosity for the apolipoprotein B X2 allele (XbaI site present) and heterozygosity for the apolipoprotein AI/CIII S2 allele (SstI site present) were associated with elevated baseline serum low-density lipoprotein cholesterol and triglyceride levels, respectively. However, the hypolipidemic effect of gemfibrozil among the responders was independent of these gene polymorphisms. These data indicate that common polymorphisms of the apolipoprotein B and apolipoprotein AI/CIII gene loci influence serum lipid levels by mechanisms that are amenable to an intervention with gemfibrozil.     

Atherogenic risk factors in cerebrotendinous xanthomatosis

In a study of coronary artery disease in patients with cerebrotendinous xanthomatosis (CTX), we documented the presence or absence of atherogenic risk factors and performed detailed analyses of serum lipid and lipoprotein profiles. Four of the seven patients examined had coronary arterial narrowing and/or obstruction, but multiple atherogenic risk factors were not found in any of these patients. Total cholesterol (T.ch) levels and low density lipoprotein-cholesterol (LDL-ch) levels were lower, and high density lipoprotein2-cholesterol (HDL2-ch) levels were higher in CTX patients than in controls. Triglyceride and very low density lipoprotein (VLDL) levels were significantly lower in the former. Indices correlating with the risk of atherosclerosis, such as the atherogenic index, and the ratios of apolipoprotein B/apolipoprotein AI, HDL2-ch/LDL-ch, HDL2-ch/HDL3-ch, indicated that CTX serum was, in fact, 'anti-atherogenic'. However, coronary artery disease is frequently seen in patients with CTX. This discrepancy suggests the existence of a unique mechanism by which atherosclerosis is induced in patients with CTX. We discuss a mechanism of disturbed lipoprotein metabolism which might be responsible for the deposition of sterols in the tissues of patients with CTX.     

慢性幽门螺杆菌感染与冠心病发病及其危险因素的关系

目的：探讨幽门螺杆菌感染与冠心病及多种危险因素的关系,观察幽门螺杆菌感染对脂质代谢、血管内皮功能、炎症介质及血清免疫学的影响.方法：应用酶联免疫吸附试验法测定冠心病组（100例）和非冠心病组（100例）血清幽门螺杆菌抗体,确证慢性幽门螺杆菌感染,分别应用酶联免疫吸附试验法及放射免疫法测定冠心病组内皮素-1.结果：（1）冠心病组血清幽门螺杆菌抗体阳性率明显高于非冠心病组（57%vs32%, P〈0.05）;（2）冠心病组慢性幽门螺杆菌感染者血浆内皮素-1水平明显高于非幽门螺杆菌感染者（P〈0.05）.结论：幽门螺杆菌慢性感染与冠心病有关,可能是冠心病发病的独立危险因索; 幽门螺杆菌慢性感染者血浆内皮素水平显著升高,可能是其导致冠心病的发病机制之一.     

Familial apolipoprotein CII deficiency: plasma lipoproteins and apolipoproteins in heterozygous and homozygous subjects and the effects of plasma infusion

Abstract. Plasma lipoproteins and apolipoproteins have been studied in a kindred with familial apolipoprotein CII (apo CII) deficiency. As in two other recently documented pedigrees, apo CII deficiency appeared to be transmitted as an autosomal recessive trait. The homozygous state was characterized by gross fasting hypertriglyceridaemia, complete absence of apo CII from plasma and failure of plasma to activate lipoprotein lipase. Post-heparin plasma hepatic triglyceride lipase activity was normal. Hypertriglyceridaemia reflected chylomicronaemia and elevated Sf 100–400 and Sf 20–100 lipoprotein concentrations; lipoproteins of Sf 12–20 (LDL₁), Sf 0–12 (LDL₂), F_1.23.5–9 (HDL₂) and F_1.20–3.5 (HDL₃) were greatly reduced in concentration. Low density lipoproteins (1.006–1.063 g/ml), isolated by preparative ultracentrifugation, and high density lipoproteins, isolated by heparin/Mn⁺⁺, were triglyceride-enriched. Electroimmunoassays revealed additionally low plasma concentrations of apolipoproteins AI, AII and B and very high concentrations of apolipoproteins CIII and E in the homozygote. The parents of the proband (heterozygotes) were normotriglyceridaemic, and had normal lipoprotein lipid concentrations and normal apolipoprotein AI, AII, B, CIII and E concentrations, in spite of having low apo CII concentrations. Activation of lipoprotein lipase in the homozygote by intravenous infusion of 200 ml fresh-frozen plasma rapidly reduced the plasma concentrations of chylomicrons and very low density lipoproteins (VLDL). Within VLDL, the decrease in concentration occurred sequentially in the Sf 100–400 and Sf 20–100 subclasses. These changes were associated during a 4-day study period with reciprocal increases in LDL₁, LDL₂, HDL₂ and HDL₃. The plasma concentrations of apo AI and apo B also increased, associated with a less marked fall in that of apo CIII; the apo AII and apo E concentrations were unchanged. These observations support other evidence that apo CII is a cofactor for the catabolism of chylomicrons and both major subfractions of VLDL by lipoprotein lipase in man, and that human LDL₁ and LDL₂ are derived, at least in part, from triglyceride-rich lipoprotein catabolism. They also suggest that both major subfractions of HDL acquire additional components during triglyceride-rich lipoprotein catabolism. In normal subjects the plasma apo CII concentration appears to be greatly in excess of that required for adequate activation of lipoprotein lipase.     

Serum apolipoproteins in heterozygous familial hypercholesterolemia.

In order to characterize the abnormalities of the lipoprotein profile in familial hypercholesterolemia (FH), serum apolipoprotein AI, AII, B, CII, CIII, and E levels were determined by the turbidimetric immunoassay in 48 patients with heterozygous FH. Apolipoprotein B levels in FH were about 2.5 fold higher (203 +/- 48 mg/dl, mean +/- S.D.) than the 30 age-matched normolipidemic control subjects (84 +/- 13 mg/dl). Significant increments of apolipoprotein CII, CIII, and E levels were observed in FH (4.6 +/- 1.6, 11.0 +/- 3.6 and 6.4 +/- 1.7 mg/dl, respectively) as compared with those in normal subjects (3.0 +/- 0.9, 7.7 +/- 1.6 and 4.5 +/- 1.1 mg/dl, respectively). Apolipoprotein AI and AII levels in FH were 130 +/- 27 and 32 +/- 6.0 mg/dl, respectively, which were not significantly different from the levels in normal subjects (131 +/- 18 and 31 +/- 5.4 mg/dl, respectively). The ratio of low density lipoprotein (LDL) cholesterol to apolipoprotein B was significantly higher in FH (1.3 +/- 0.3) than that in normal subjects (1.2 +/- 0.1). This indicates that the LDL of FH was cholesterol-rich in comparison with that of normal subjects. The ratio of high density lipoprotein (HDL) cholesterol to apolipoprotein AI in FH (0.34 +/- 0.07) was significantly lower than that in normal subjects (0.39 +/- 0.05). This difference might possibly be produced by an abnormal HDL metabolism of FH patients, a topic which remains to be elucidated by further investigation.     

Fibrates

Fibrates regulates not only plasma lipid metabolism but vascular biology by activating nuclear receptor peroxisome proliferating activated alpha (PPAR alpha). Major effects on plasma lipid levels are lowering plasma triglyceride level and elevating plasma HDL cholesterol level, whereas its effect on plasma cholesterol level is moderate compared to HMG-CoA reductase inhibitor. As a mechanism for its effects on plasma lipid levels and atherosclerosis, recent studies reported that fibrates activates various genes involved in metabolism of remnants and HDL such as lipoprotein lipase, apo AI, apo AII, and apo CIII genes through the interaction with PPAR alpha, lowering atherogenic lipoproteins and elevating anti-atherogenic lipoproteins. Furthermore, fibrates may influence the process of atherosclerosis by modifying inflammatory process in vascular wall. Recent clinical studies demonstrated that fibrates significantly reduce cardiovascular events in patients with either hypertriglyceridemia or low HDL cholesterol level.     

Post-heparin plasma lipoprotein lipase, but not hepatic lipase activity, is related to plasma adiponectin in type 2 diabetic patients and healthy subjects

The aim of this study was to determine the relationships of plasma adiponectin with post-heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities, and to evaluate whether plasma adiponectin contributes to diabetes-associated dyslipidaemia. Plasma adiponectin, post-heparin plasma lipase activities, lipoproteins and insulin sensitivity (hyperinsulinaemic euglycaemic clamp) were measured in 24 male type 2 diabetic patients and 24 age-matched healthy men. Plasma triglycerides (P < 0.01) and apolipoprotein B levels (P < 0.01) were higher, and HDL cholesterol was lower (P < 0.05) in type 2 diabetic patients. Plasma adiponectin, as well as LPL and HL activities were not significantly different between diabetic and healthy subjects. Multiple regression analysis showed that LPL activity was positively related with plasma adiponectin (P < 0.05). In contrast, HL activity was positively related with body mass index (P < 0.02) and waist/hip ratio (P < 0.05, multiple r = 0.74), but not with plasma adiponectin. Plasma adiponectin was positively associated with insulin sensitivity (P = 0.001), age (P < 0.02) and LPL activity (P < 0.05, multiple r = 0.64), but not with the presence of diabetes and HL activity. Plasma triglycerides were negatively related with LPL activity (P = 0.002) and positively with the diabetic state (P = 0.001, multiple r = 0.58). HDL cholesterol was positively related with plasma adiponectin (P = 0.003) and negatively with HL activity (P < 0.02) as well as with the presence of diabetes (P = 0.05, multiple r = 0.59). We conclude that post-heparin plasma LPL activity, but not HL activity, is related with plasma adiponectin. Plasma adiponectin appears to be a determinant of plasma triglycerides via an effect on LPL activity. It seems unlikely that plasma adiponectin predicts the effects of the diabetic state as such on high plasma triglycerides and low HDL cholesterol.     

Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo.

Previous data suggest that apolipoprotein (apo) CIII may inhibit both triglyceride hydrolysis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CIII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of 125I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of [3H]glycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal. In vitro experiments indicated that, although sera from the apo CIII-apo-AI deficient patients were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoprotein lipase.     

血清脂质、脂蛋白胆固醇和载脂蛋白在冠心病中的临床意义

目的研究冠心病患者的血清脂质、脂蛋白胆固醇和载脂蛋白的变化、辨别力和诊断价值。方法测定64例冠心病(CHD)患者和60例正常人的血脂、脂蛋白胆固醇和载脂蛋白,并比较计算其辨别力和诊断价值。结果和结论冠心病患者的TC(女)、TG、LDL-C、ApoB、LDL-C/HDL-C和ApoB/ApoAI明显高于正常人(P<0.05),HDL2-C、HDL3-C、HDL-C、ApoAI和HDL-C/TC明显低于正常人(P<0.05)。由HDL-C、TC和TG血脂三项可代替HDL-C、LDL-C、VLDL-C、TC和TG血脂五项,对冠心病的诊断目前有应用价值,若加上HDL2-C和HDL3-C或ApoAI和ApoB,则对冠心病的诊断更有意义。     

Do mutations causing low HDL-C promote increased carotid intima-media thickness?

BACKGROUND: Although observational data support an inverse relationship between high-density lipoprotein (HDL) cholesterol and coronary heart disease (CHD), genetic HDL deficiency states often do not correlate with premature CHD. METHODS: Carotid intima-media thickness (cIMT) measurements were obtained in cases comprising 10 different mutations in LCAT, ABCA1 and APOA1 to further evaluate the relationship between low HDL resulting from genetic variation and early atherosclerosis. RESULTS: In a 1:2 case-control study of sex and age-related (+/-5 y) subjects (n=114), cIMT was nearly identical between cases (0.66+/-0.17 cm) and controls (0.65+/-0.18 cm) despite significantly lower HDL cholesterol (0.67 vs. 1.58 mmol/l) and apolipoprotein A-I levels (96.7 vs. 151.4 mg/dl) (P<0.05) CONCLUSIONS: Genetic variants identified in the present study may be insufficient to promote early carotid atherosclerosis.     

Study of DNA polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster in patients with peripheral arterial disease

1. We have determined the frequency of DNA polymorphisms of the human apolipoprotein AI-CIII-AIV gene cluster, detected with XmnI, PstI, and PvuII, in a group of patients with peripheral arterial disease. 2. Of the patients, 81 had no evidence of disease in the coronary and carotid arteries, 73 had coronary artery disease but no evidence of carotid artery disease, 25 patients had carotid artery disease but no evidence of coronary artery disease, and 38 had both coronary and carotid artery disease. 3. Levels of triacylglycerol, cholesterol, apolipoprotein B and apolipoprotein AI were not significantly different between the four patient groups. 4. The frequencies of the alleles for the apolipoprotein AI-CIII-AIV polymorphisms, detected with XmnI, PstI and PvuII, did not differ significantly in the patient groups when compared with a sample of clinically well normolipidaemic individuals also from a London population. 5. All five patients with the XmnI genotype we designate X2X2 had high levels of cholesterol, apolipoprotein B and apolipoprotein AI. 6. Patients with the rare VB2 allele of the apolipoprotein CIII-AIV restriction fragment length polymorphism had lower levels of cholesterol, acylglycerol and significantly lower levels of serum apolipoprotein. 7. Our observations suggest that variation in the apolipoprotein AI-CIII-AIV gene cluster may not be contributing significantly to the development of peripheral arterial disease, but variation associated with some of the restriction fragment length polymorphisms may be involved in determining levels of cholesterol- and apolipoprotein-B-containing lipoproteins.     

Effect of alcohol on lipids and lipoproteins in relation to atherosclerosis

Several studies indicate that light-to-moderate alcohol consumption is associated with a low prevalence of coronary heart disease. An increase in high-density lipoprotein (HDL) cholesterol is associated with alcohol intake and appears to account for approximately half of alcohol's cardioprotective effect. In addition to changes in the concentration and composition of lipoproteins, alcohol consumption may alter the activities of plasma proteins and enzymes involved in lipoprotein metabolism: cholesteryl ester transfer protein, phospholipid transfer protein, lecithin:cholesterol acyltransferase, lipoprotein lipase, hepatic lipase, paraoxonase-1 and phospholipases. Alcohol intake also results in modifications of lipoprotein particles: low sialic acid content in apolipoprotein components of lipoprotein particles (e.g., HDL apo E and apo J) and acetaldehyde modification of apolipoproteins. In addition, "abnormal" lipids, phosphatidylethanol, and fatty acid ethyl esters formed in the presence of ethanol are associated with lipoproteins in plasma. The effects of lipoproteins on the vascular wall cells (endothelial cells, smooth muscle cells, and monocyte/macrophages) may be modulated by ethanol and the alterations further enhanced by modified lipids. The present review discusses the effects of alcohol on lipoproteins in cholesterol transport, as well as the novel effects of lipoproteins on vascular wall cells.