Studies on Hyperlipoproteinemic Trait, Especially Plasma Apolipoprotein Mutants, as a Risk Factor for Atherosclerosis

1.用中国仓鼠卵巢细胞通过基因工程技术制备了载脂蛋白E突变体E5和E7。这些结果与血浆中的结果高度一致。我们研究了载脂蛋白E5和E7在血浆脂蛋白中的分布，以及这些突变体的肝素结合活性。载脂蛋白E5和载脂蛋白E7在VLDL组分中比在HDL组分中更显著。载脂蛋白E7与肝素的相互作用强于载脂蛋白E3。2.载脂蛋白B和低密度脂蛋白的结合我们分析了高脂蛋白血症患者的LDL与LDL受体的结合亲和力。本研究未发现家族性载脂蛋白B-100（Arg_<3500>*Gin）缺陷。然而，来自高胆固醇血症患者的LDL显示出对LDL受体的低亲和力。低密度脂蛋白富含蛋白质，缺乏脂质， 关于我们 低于对照组的LDL。这些结构和功能异常可通过药物治疗逆转，强调了治疗高脂血症对预防动脉粥样硬化的重要性。3.脂蛋白（a）作为动脉粥样硬化的危险因素我们研究了脂蛋白（a）[Lp（a）]与动脉粥样硬化的关系。即使在胆固醇正常的受试者中，血清Lp（a）升高也与动脉粥样硬化有关，并影响其严重程度。虽然据报道，载脂蛋白（a）的大小和血浆Lp（a）浓度之间存在反比关系，但我们发现每种载脂蛋白（a）亚型的Lp（a）值变化很大。4.动脉粥样硬化动物模型中的载脂蛋白A-1和载脂蛋白A-IV我们建立了兔载脂蛋白A-1和载脂蛋白A-IV的酶免疫分析方法。Watanabe遗传性高脂血症兔（WHHL-R）可引起载脂蛋白A-I和载脂蛋白A-IV水平降低，载脂蛋白A-IV在WHHL-R中的分布向脂蛋白A-1和载脂蛋白A-IV的方向移动，并可使载脂蛋白A-1和载脂蛋白A-IV的水平降低。免费游泳池。这些结果表明胆固醇在WHHL-R中的反向转运受损。我们研究了重组高密度脂蛋白（r-HDL）对动脉粥样硬化的影响。注射r-HDL对动脉粥样硬化形成有轻微的抑制作用，但两种变化均无统计学意义，表明动脉粥样硬化和天然脂蛋白的生理特性可能不同。少

1.Applipoprotein E Mutants and Lipoprotein MetabolismApo E mutants, E5 and E7, were produced by Chinese hamster ovary cells by means of gene technology. They were highly consistent with those obtained from plasma. We investigated the distribution of apo E5 and apo E7 among the plasma lipoproteins, and the heparin-binding activities of these mutants. Both apo E5 and apo E7 were more prominent in the VLDL fraction than in the HDL fraction. Apo E7 displayd a stronger interaction with heparin than apo E3. This may be one of the mechanisms producing atherosclerotic disease in patients with the apo E7 mutant.2.Abnormalities of Apolipoprotein B and Low Density LipoproteinWe analyzed the binding affinity of LDL from patients with hyperlipoproteinemia to the LDL receptor. Familial defective apo B-100 (Arg_<3500>*Gin) was not found in the present study. However, LDL from patients with hypertriglyceridemia showed a low affinity to the LDL receptor. The LDL was rich in protein, poor in lipids, and … More smaller than LDL from controls. These structural and functional abnormalities were reversed by drug therapy, emphasizing the importance of treating hypertriglyceridemia for the prevention of atherosclerosis.3.Lipoprotein (a) as a Risk Factor for AtherosclerosisWe investigated the association between Lipoprotein (a) [Lp (a) ] and atherosclerosis. Even in normocholesterolemic subjects, elevated serum Lp (a) was linked to atherosclerosis and influenced its severity. While it is reported that there is an inverse relationship between the size of apo (a) and plasma Lp (a) concentrations, we found wide variations of Lp (a) values in each apo (a) isoform. Our results suggested that apo E phenotype may be one of other factors influencing the plasma Lp (a) concentration.4.Apo A-1 and Apo A-IV in animal models for AtherosclerosisWe developed a enzyme immunoassay for rabbit apo A-I and apo A-IV.Watanabe heritable hyperlipidemic rabbit (WHHL-R) caused reduced levels of apo A-I and apo A-IV.The distribution of apo A-IV in WHHL-R was shifted towards the lipoprotein-free pool. These results show an impaired reverse transport of cholesterol in WHHL-R.We investigated the effects of reconstituted high-density lipoprotein (r-HDL) on atherosclerosis. Injection of r-HDL caused slight inhibition of atherogenesis, but neither change was statistically significant, indicating that the physiological properties of artficial and nativelipoproteins may differ. Less