Platelet and atherosclerosis, with special reference to interaction between platelets and lipoproteins.

血小板和动脉粥样硬化，特别是血小板和脂蛋白之间的相互作用。

基本信息

批准号：
02454515
负责人：
KUME Shoji
金额：
$ 1.22万
依托单位：
Yamanashi Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

1) Effect of low-density lipoprotein (LDL) on platelet function. LDL(d=1.019-1.050) binds to human platelets with the dissociation constant (Kd) of 58nM and 1750 binding sites per platelet. LDL at a concentration under 1mg/ml induces a transient increase in intracellular Ca^<2+> concentration and a shape change of human platelets, but does not release granules, induce thromboxane B_2 formation or protein phosphorylation. LDL at a concentration of 100mug/ml which is near Kd of LDL-binding had a maximal stimulatory effect on agonist-induced platelet aggregation. LDL binding on platelets is Ca^<2+>-independent and displaced by high density lipoprotein (HDL). These results suggest that LDL enhances agonist-induced platelet activation via platelet-type LDL receptors differing from classical LDL receptors.2) Effect of high-density lipoprotein (HDL) on platelet function Apolipoprotein E -(ApoE-) rich HDL of normal subjects and hyperalphalipoproteinemic patients, showed marked inhibitory effects on platelet aggregation and ATP release as compared with apoE-poor HDL, suggesting that apoE has inhibitory effects on platelet function. Dimyristoyl phosphatidylcholine liposome with apoE (apoE・DMPC) also inhibited platelet aggregation, and incubation of washed platelets with apoE・DMPC resulted in the release of cholesterol into the supernatant. These results suggest that apoE plays a major role in the inhibitory effect of apoE-rich HDL on platelet function, presumably due to the release of cholesterol from the plasma membrane.

1）低密度脂蛋白（LDL）对血小板功能的影响。 LDL（d = 1.019-1.050）与每个血小板的分离常数（KD）结合，分离常数（KD）为1750个结合位点。在1mg/ml下的浓度下的LDL诱导细胞内Ca^<2+>浓度的短暂增加和人血小板的形状变化，但不会释放颗粒，诱导血栓烷B_2形成或蛋白质磷酸化。在LDL结合的KD附近的100毫升浓度下的LDL对激动剂诱导的血小板聚集具有最大的刺激作用。 LDL在血小板上的结合是Ca^<2+> - 独立的，并由高密度脂蛋白（HDL）移位。 These results suggest that LDL enhances agonist-induced platelet activation via platelet-type LDL receptors differentiating from classic LDL receptors.2) Effect of high-density lipoprotein (HDL) on platelet function Apolipoprotein E -(ApoE-) rich HDL of normal subjects and hyperalphalipoproteinemic patients, shown marked inhibitory effects on platelet aggregation and ATP release as compared with ApoE贫乏的HDL表明APOE对血小板功能具有抑制作用。 Dimerristoyl磷脂酰胆碱与APOE（APOE ・DMPC）也抑制了血小板聚集，并将洗涤后的血小板与APOE ・DMPC孵育导致胆固醇释放到超级中心中。这些结果表明，APOE在富含APOE的HDL对血小板功能的抑制作用中起主要作用，这可能是由于胆固醇从质膜中释放出来。