A modern view of atherogenesis.
A modern view of atherogenesis.
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动脉粥样硬化形成的现代观点。
DOI：
10.1016/0002-9149(93)90139-4
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Sprague,EA
中科院分区：
文献类型：
--
作者：
Schwartz,CJ;Valente,AJ;Sprague,EA
动脉粥样硬化级联反应中的两个关键事件是低密度脂蛋白(LDL)胆固醇在动脉部位的局灶性流入和积聚，这有利于动脉粥样硬化病变的发展，以及血液单核细胞向这些病变易发部位的募集。在高脂血症和血脂异常的情况下，这两个过程都会增强。被招募到内皮表面的单核细胞随后在趋化物质的指导下迁移到内皮下间隙，如单核细胞趋化蛋白-1和氧化修饰的低密度脂蛋白。然后，这些细胞经过激活-分化成为巨噬细胞。与此同时，低密度脂蛋白，可能还有其他脂蛋白，如致密的小颗粒低密度脂蛋白和脂蛋白(A)，穿过血管内皮细胞，经历活性氧的氧化修饰。这些氧化修饰的脂蛋白可被非下调的巨噬细胞清道夫受体识别。它们被这些受体摄取，导致形成具有早期动脉粥样硬化特征的泡沫细胞。随着单核细胞募集和脂蛋白流入的继续，病变生长并发展为脂肪条纹。随后，由于细胞毒性氧化修饰的低密度脂蛋白的影响，泡沫细胞坏死，内膜平滑肌细胞胶原合成增加，导致已建立的动脉粥样硬化病变，称为纤维斑块。随着我们对动脉粥样硬化发病机制的了解在过去几年中不断发展，出现了干预动脉粥样硬化形成过程的新策略。
Two key events in the atherogenic cascade are the focal influx and accumulation of low-density lipoprotein (LDL) cholesterol at arterial sites having a predilection for atherosclerotic lesion development and the recruitment of blood monocytes to these lesion-prone sites. Both processes are enhanced in the setting of hyperlipidemia and dyslipoproteinemia. The monocytes recruited to the endothelial surface subsequently migrate to the subendothelial space under the directed guidance of chemoattractants, such as monocyte chemotactic protein-1 and oxidatively modified LDL. These cells then undergo activation-differentiation to become macrophages. At the same time, LDL, and probably other lipoproteins such as the small dense LDL particles and lipoprotein (a), traverse the endothelium and undergo oxidative modification by reactive oxygen species. These oxidatively modified lipoproteins are recognizable by the non-down-regulating macrophage scavenger receptor. Their uptake by these receptors results in the formation of the foam cell characteristic of early-stage atherosclerosis. As monocyte recruitment and lipoprotein influx continue, the lesion grows and develops into the fatty streak. Subsequent foam cell necrosis due to the influence of cytotoxic oxidatively modified LDL and increased collagen synthesis by intimal smooth muscle cells lead to the established atherosclerotic lesion referred to as the fibrous plaque. As our understanding of the mechanisms involved in the pathogenesis of atherosclerosis has evolved over the past few years, novel strategies for intervention in the atherogenic process have emerged.