RELEASE OF CHOLESTEROL FROM ACTIVATED PLATELETS

从活化的血小板中释放胆固醇

• 批准号: 3966657
• 负责人: H S KRUTH
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3966657
• 关键词: atherosclerosis; cholesterol; cholesterol esters; human tissue; pathologic process; platelet aggregation; stainings; thrombin; thrombosis; vascular smooth muscle

Cholesterol accumulation by cells in the blood vessel wall or in thrombi associated with blood vessels is the hallmark of the atherosclerotic lesion. Previous work in our laboratory has shown that platelets can medicate cholesterol accumulation in vascular smooth muscle cells. This study shows that when platelets are activated, they release cholesterol. Washed human or rat platelets, activated with the potent platelet agonist thrombin, released 50 nmoles of cholesterol per 3 billion platelets. This amount represents approximately 20 percent of the platelet cholesterol content. The calcium ionophore, A23187 (5 Mum) was as effective as thrombin in stimulating cholesterol release, whereas, collagen (200 Mug/ml, type I) was somewhat less effective. ADP (200 Mum), a less potent platelet agonist, was ineffective in stimulating cholesterol release. The release of cholesterol from activated platelets was relatively slow (less than 90% released within 2 hours) when compared with the rapid release of serotonin (less than 90% released within 5 min) a constituent of dense granules. Release of cholesterol was inhibited by the platelet antagonist forskolin, an agent that elevates platelet cAMP. Release of cholesterol could be dissociated from release of a cytoplasmic marker lactate dehydrogenase suggesting that cholesterol release did not result simply from platelet lysis. These findings suggest that platelets, in addition to their known function of stimulating proliferation of cells, are also a source of cholesterol that may accumulate in cells. Both of these platelet functions are relevant to the pathogenesis of atherosclerosis, a disease in which cell proliferation and cellular accumulation of cholesterol are characteristic.

胆固醇在血管壁或血栓中的细胞积聚 是动脉粥样硬化的标志 损伤。 我们实验室之前的工作表明，血小板可以 胆固醇在血管平滑肌细胞中积聚。 这 研究表明，当血小板被激活时，它们会释放胆固醇。 洗涤过的人或大鼠血小板，用强效血小板激动剂活化 凝血酶，每30亿血小板释放50纳摩尔胆固醇。 这 约占血小板胆固醇的20% 内容 钙离子载体A23187（5 μ m）与 凝血酶刺激胆固醇释放，而胶原蛋白（200 μ g/ml， I型）的效果稍差。 ADP（200 μ m），效力较低的血小板 激动剂，在刺激胆固醇释放方面无效。 活化血小板释放胆固醇相对缓慢 (less 90%以上在2小时内释放）， 5-羟色胺的释放（5分钟内释放不到90%）， 致密颗粒 血小板抑制胆固醇的释放 拮抗剂毛喉素，一种提高血小板cAMP的药物。 释放 胆固醇可以从细胞质标记物的释放中分离出来， 乳酸脱氢酶表明胆固醇释放没有导致 仅仅是血小板溶解。 这些发现表明，血小板，除了其已知的功能， 也是胆固醇的来源 可能会在细胞中积累。 这两种血小板功能都是 与动脉粥样硬化的发病机制有关，动脉粥样硬化是一种细胞 胆固醇的增殖和细胞积累是特征。