The HGAR1 familial hypercholesterolemia pedigree

Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley-Liss, Inc.     

Homocysteinylation of low-density lipoproteins (LDL) from subjects with Type 1 diabetes: effect on oxidative damage of human endothelial cells.

BACKGROUND: Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). Individuals with Type 1 and Type 2 diabetes are more susceptible to the effects of homocysteine than non-diabetic subjects. The interaction between homocysteine-thiolactone (Hcy-thiolactone), a reactive product of Hcy, and low-density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL) and it has been suggested that homocysteinylation could increase atherogenicity of lipoproteins. AIM: The aim of the study was to compare the effect of in vitro homocysteinylation of LDL isolated from healthy control subjects (C-LDL) and from Type 1 diabetic patients (DM-LDL) and to investigate the effect of homocysteinylated LDL (Hcy-C-LDL and Hcy-DM-LDL) on peroxynitrite production of endothelial cells. METHODS: The in vitro homocysteinylation of LDL isolated from control (n = 12) and DM subjects (n = 12) was carried out by incubating lipoproteins with Hcy-thiolactone. The reaction was verified by quantifying the increase in sulphydryl groups (-SH groups) in Hcy-LDL with respect to control LDL. Control and homocysteinylated LDL were incubated with human aortic endothelial cells (HAEC) in culture. Peroxynitrite production in cells treated in different experimental conditions was assayed by a fluorimetric method. RESULTS: The increase in -SH groups after incubation with homocysteine was greater in LDL from diabetic subjects compared with LDL from control subjects (P < 0.001). In addition, peroxynitrite production from HAEC incubated with Hcy-LDL from diabetic patients was greater than after incubation with Hcy-LDL from control subjects and untreated LDL from diabetic patients (P < 0.001). CONCLUSIONS: These results show that LDL from diabetic patients is more susceptible to in vitro homocysteinylation than LDL from non-diabetic individuals and demonstrate that the compositional changes in Hcy-LDL from diabetic subjects have cytotoxic effects on human endothelial cells.     

Cardiovascular regulation and lipoprotein profile during administration of co-dergocrine in essential hypertension

Summary Co-dergocrine has recently been demonstrated acutely to lower plasma norepinephrine (NE) and blood pressure (BP) in patients with essential hypertension, and similar results have been obtained during chronic administration of co-dergocrine to healthy men. The present study investigated the effect of 3 weeks of treatment with co-dergocrine 4 mg/day on BP, plasma catecholamines, certain other BP-regulating factors and serum lipoproteins in patients with essential hypertension. Compared to placebo conditions, co-dergocrine decreased supine BP and heart rate by −7% and the upright plasma NE level by −24%. Supine plasma NE also fell (−24%). Total cholesterol and the LDL + VLDL-cholesterol lipoprotein fraction were lowered by −6%. No significant change was observed in plasma renin activity, angiotensin II, aldosterone and epinephrine levels, whole blood and plasma volume, exchangeable sodium, and the cardiovascular responsiveness to NE, angiotensin II and isoproterenol. The findings suggest that in patients with essential hypertension, chronic treatment with co-dergocrine may slightly decrease sympathetic outflow and, at least in the short-term, lower the potentially atherogenic serum LDL + VLDL − cholesterol fraction.     

Association of a genetic polymorphism in human apolipoprotein B-100 with intermediate density lipoprotein concentrations

Immunochemical techniques have been used to identify five antigenic (Ag) sites on apolipoprotein B-100 (apoB), the major protein constituent of very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL). Each Ag site results from allelic variation at a specific locus of the apoB gene. In the present study, we assessed whether variations in the five Ag loci were associated with concentrations of plasma lipids or lipoprotein fractions measured by analytical ultracentrifugation in a group of 44 healthy men. Pair-wise analyses of the Ag markers revealed that Ag(a1/d), in association with either Ag(x/y) or Ag(t/z), is significantly related to plasma IDL-mass concentrations. In this cohort we detected no significant associations of the Ag alleles (singly or in combination) with plasma total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, or mass of total VLDL or LDL. These results suggest that genetic variations in the apoB molecule may predispose to variations in concentrations of IDL that could have consequences for atherosclerotic risk.     

冠心病病人氧化修饰低密度脂蛋白的测定及临床意义

目的 :探讨氧化修饰低密度脂蛋白 (Ox LDL)对冠心病 (CHD)形成和发展的影响。方法 :CHD组 6 0例 ,对照组 5 3例。用酶标多克隆抗体夹心的方法检测血清Ox LDL含量。结果 :CHD组血清Ox LDL含量为 ( 48.6± 32 .8) μg dl。对照组( 2 5 .9± 2 2 .5 ) μg dl,两组之间Ox LDL含量存在显著性差异 (P <0 .0 0 1)。 结论 :Ox LDL和CHD有密切的关系 ,故可作为CHD病人特异性的辅助诊断指标。     

Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism

Abstract. The mechanisms responsible for the decreased high density lipoprotein (HDL) cholesterol levels associated with obesity and insulin resistance are not well understood. Lecithin: cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein (CETP) are key factors in the esterification of cholesterol in HDL and the subsequent transfer of cholesteryl ester towards apolipoprotein B-containing lipoproteins. Phospholipid transfer protein (PLTP) may be involved in the regulation of HDL particle size. We therefore measured the activities of LCAT, CETP and PLTP using exogenous substrate assays, as well as lipids, lipoproteins, insulin and C-peptide in fasting plasma from eight healthy obese men (body mass index >27 kg m^-2) and 24 non-obese subjects. The obese men had lower levels of HDL cholesterol (P<0·05) and higher levels of plasma triglycerides (P<0·05), insulin (P<0·05) and C-peptide (P<0·01), as compared to the quartile of subjects with the lowest body mass index (BMI <22·4 kg m^-2). CETP and PLTP activities were elevated in the obese men by 35% (P<0·01) and by 15% (P<0·05), respectively. LCAT activity was comparable among the quartiles. Linear regression analysis showed that CETP activity was positively correlated with body mass index (P<0·02), fasting blood glucose (P7lt;0·05) and plasma C-peptide (P<0·05). PLTP activity was positively related to body mass index (P<0·01), waist to hip circumference ratio (P<0·001), as well as to fasting blood glucose (P<0·05) and plasma C-peptide (P<0·05) It is concluded that the activities of CETP and PLTP are influenced by adiposity and possibly by insulin resistance. Elevated lipid transfer protein activities may provide a mechanism that contributes to alterations in HDL in insulin resistant states.     

脑梗死患者血浆氧化低密度脂蛋白与一氧化氮、假性血友病因子及血浆颗粒膜蛋白的关系研究

目的探讨动脉粥样硬化性脑梗死患者血浆氧化低密度脂蛋白与血管内皮损伤及血小板活化程度的关系。方法用酶联免疫吸附测定（ELISA）的方法检测49例脑梗死患者和50例相匹配的对照组血浆氧化低密度脂蛋白（OX-LDL）、血管性假血友病因子（VWF）、血浆颗粒膜蛋白（GMP-140）水平，同时用硝酸还原酶比色法测定血清一氧化氮（NO）水平，并把、VWF、GMP-140、NO与OX-LDL作相关分析。结果脑梗死组血浆OX-LDL、、VWF、GMP-140明显高于对照组（t=2．91，P〈0．01；t=3．94，P〈0．001；t=2．08，P〈0．05），而脑梗死组血清NO水平明显低于对照组（t=4．02，P〈0．001）；相关分析表明血浆OX-LDL水平与血清NO水平呈负相关（r=-0．204，P〈0．05），与血浆懈呈正相关（r=0．60，P〈0．01），与血浆GMP-140呈正相关（r=0．430，P〈0．01）。结论脑梗死患者的血浆OX-LDL明显增高，而OX-LDL增高可能是脑梗死的危险因素。     

The distribution profiles of very low density and low density lipoproteins in poorly-controlled male,Type 2 (non-insulin-dependent) diabetic patients

Summary The distribution and composition of lipoproteins spanning the very low density and low density lipoprotein spectra have been analysed in ten poorly-controlled, male, Type 2 (non-insulin-dependent), diabetic patients pre-disposed to mild, secondary hypertriglyceridaemia. As compared to age-matched control subjects, the diabetic patients displayed grossly modified, distinctly atherogenic lipoprotein profiles. Modifications were not limited to the very low density lipoprotein profile, as would be expected from the pre-treatment hypertriglyceridaemia. There was also an aberrant low density lipoprotein profile, which was not evident from plasma cholesterol measurements, especially as the diabetic patients at entry were well matched to control subjects with respect to plasma levels of this lipid. Compositional abnormalities were also observed in the poorly-controlled diabetic group, although these were less marked than the distributional changes. There were substantial improvements of the abnormalities detailed above, even over a short treatment period (two weeks), with therapy designed primarily to ameliorate metabolic control. The data suggest that, in the presence of poor metabolic control and hypertriglyceridaemia, occult, atherogenic modifications of low density lipoproteins can occur. The results argue in favour of strict control of triglyceride levels even in diabetic patients with apparently acceptable cholesterol levels.