PLATELET-MEDIATED CHOLESTEROL ACCUMULATION WITHIN VASCULAR-ASSOCIATED CELLS

血管相关细胞内血小板介导的胆固醇积累

• 批准号: 4694613
• 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/4694613
• 关键词: atherosclerosis; cholesterol; cholesterol esters; pathologic process; platelet aggregation; stainings; thrombin; thrombosis; vascular smooth muscle

The purpose of this project is to examine mechaniams of cellular cholesteryl ester accumulation that may be mediated by platelets. Washed rate platelets have been incubated with smooth muscle cells, macrophages, fibroblasts, and endothelian cells. In addition, platelet-free supernatants, prepared from unactivated or activated incubated platelets have been added to cultures of these cells. As reported last year, activated rat platelets induce cholesteryl ester accumulation in cultured rate aortic smooth muscle cells. We have determined this year that platelet activation by collagen is equally effective as is platelet activation with thrombin. Histochemical detection of smooth muscle cholesteryl ester accumulation has been confirmed chemically as platelet-mediated stimulation of cholesteryl ester synthewsis. Interestingly, cholesteryl ester accumulates in a subpopulation of cultured human aortic smooth muscle cells, suggesting that smooth muscle cells may be comprised of at least two functional subtypes with respect to platelet-mediated cholesterol accumulation. We have also determined that platelets release substantial amounts of unesterified cholesterol when they are activated. Cholesterol release is calcium dependent and can be totally or partially blocked by a variety of anti-platet drugs. The possible role of platelets in promoting smooth muscle cell proliferation within atherosclerotic lesions has been previously recognized. Our research has shown that platelet can mediate cholesteryl ester accumulation within cultured vascular-derived smooth muscle cells. The possible role of platelets in mediating cholesterol accumulation within atherosclerotic lesions must now also be considered in evaluating the pathogenesis of atherosclerosis.

这个项目的目的是研究细胞的机制。 可能由血小板介导的胆固醇酯蓄积。洗过了 血小板与平滑肌细胞、巨噬细胞、 成纤维细胞和内皮细胞。此外，不含血小板 从未激活或激活的孵化血小板制备的上清液 已经加入到这些细胞的培养中。 据去年报道，激活的大鼠血小板可诱导胆固醇酯 在培养的大鼠主动脉平滑肌细胞中积聚。我们有 今年确定了胶原蛋白对血小板的激活作用 凝血酶激活血小板也是有效的。组织化学检测 已证实平滑肌胆固醇酯蓄积 作为血小板介导的胆固醇酯刺激的化学作用 合成。有趣的是，胆固醇酯在 培养的人主动脉平滑肌细胞亚群，提示 平滑肌细胞可能由至少两种功能亚型组成 与血小板介导的胆固醇积聚有关。 我们还确定，血小板会释放大量的 当未酯化的胆固醇被激活时。胆固醇的释放是 钙依赖，可被多种药物完全或部分阻断 抗血小板药物。 血小板在促进平滑肌细胞生长中的可能作用 动脉粥样硬化病变内的增殖以前 被认可了。我们的研究表明，血小板可以调节胆固醇 培养的血管来源的平滑肌细胞中的酯积累。 血小板在体内调节胆固醇蓄积中的可能作用 动脉粥样硬化损害现在也必须被考虑在评估 动脉粥样硬化的发病机制。