Ardlie N G, Selley M L, Simons L A
Division of Clinical Sciences, John Curtin School of Medical Research, Australian National University, Canberra.
Atherosclerosis. 1989 Apr;76(2-3):117-24. doi: 10.1016/0021-9150(89)90094-4.
Interactions between altered lipoproteins and platelets may be important in atherosclerosis lesion formation and thrombosis. The aims of this study were to compare the effects of oxidatively modified and native low density lipoproteins (LDL) and high density lipoproteins (HDL) on platelet responses in the presence and absence of other platelet agonists, and investigate the mechanism(s) by which lipoproteins influence platelet activation. We have shown that native and oxidatively modified lipoproteins differ importantly in their effects on platelets; oxidation renders lipoproteins more reactive to platelets. Native LDL promote aggregation of human platelets, enhance the mobilization of arachidonate from phospholipids, increase thromboxane B2 production, and decrease membrane fluidity. Oxidized LDL are more reactive than native LDL and alone cause aggregation. Native HDL inhibit platelet responses and increase membrane fluidity. Oxidized HDL promote aggregation and cause spontaneous aggregation. The enhanced platelet responses cannot be attributed to increased production of thromboxane A2 since cyclooxygenase inhibitors (aspirin, indomethacin) have little inhibitory effect. The data suggest that activation of platelets by lipoproteins results from changes in membrane fluidity. These observations shed new light on the potential role of altered lipoproteins in the pathogenesis of atherosclerosis and its complications.
脂蛋白改变与血小板之间的相互作用在动脉粥样硬化病变形成和血栓形成中可能起重要作用。本研究的目的是比较氧化修饰的和天然的低密度脂蛋白（LDL）及高密度脂蛋白（HDL）在有或无其他血小板激动剂存在时对血小板反应的影响，并研究脂蛋白影响血小板活化的机制。我们已经表明，天然的和氧化修饰的脂蛋白对血小板的作用有重要差异；氧化使脂蛋白对血小板更具反应性。天然LDL促进人血小板聚集，增强花生四烯酸从磷脂的动员，增加血栓素B2的产生，并降低膜流动性。氧化LDL比天然LDL更具反应性，单独即可引起聚集。天然HDL抑制血小板反应并增加膜流动性。氧化HDL促进聚集并引起自发聚集。血小板反应增强不能归因于血栓素A2产生增加，因为环氧化酶抑制剂（阿司匹林、吲哚美辛）几乎没有抑制作用。数据表明，脂蛋白对血小板的活化是由膜流动性的变化引起的。这些观察结果为改变的脂蛋白在动脉粥样硬化发病机制及其并发症中的潜在作用提供了新的线索。
