动脉粥样硬化的发生机制技术报告.ppt

LDL LDL 内皮 管腔 单核细胞 巨噬细胞 黏附分子 巨噬细胞和泡沫细胞进的炎症放大作用 泡沫细胞 内膜 修饰的 LDL Ross R. N Engl J Med. 1999;340:115-126. MCP-1 趋化因子 动脉粥样硬化脂纹期 内皮下聚集的大量泡沫细胞 内皮 管腔 单核细胞 巨噬细胞 平滑肌细胞的迁移、增殖 泡沫细胞 内膜 Cell ProliferationMatrix Degradation 趋化因子 生长因子 (PDGF/FGF/TGF-à） Ross R. N Engl J Med. 1999;340:115-126. 中膜 平滑肌细胞分化和合成 细胞外基质 胶原纤维 蛋白多糖 弹力蛋白 Differentiation of monocytes into macrophages The modified LDL plays an important role in promoting the differentiation of monocytes into macrophages, a key step in the inflammatory process on the way to the development of atherosclerosis. Reference: Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med 1989;320:915-924. 数分钟 2小时 Following rapid induction of hypercholesterolemia in rabbits due to injection of LDL, the earliest detectable change in the arterial wall is the intramural retention of LDL and of microaggregates of LDL, a change that occurs within 2 hours.46 Perfusion of arterial segments in situ has shown substantial accumulation of LDL within 5 minutes.31 Early arterial retention of injected LDL in vivo is focal, in sites that are known to be susceptible to the subsequent development of atheromata. This accumulation of lipoproteins in the intima is dependent on the balance between the rates at which they enter and leave the arterial wall and the rate at which they are degraded within it. Studies in humans, rabbits, and pigs suggest that influx of lipoproteins into the intima increases directly with increasing lipoprotein concentration in plasma9 10 and decreases inversely with increasing lipoprotein diameter.10 11 12 13 14 Very large lipoproteins, with diameters >75 nm, seem to be excluded from the intima Nevertheless, the status of proteoglycans, LpL, sphingomyelinase(Smase), and possibly other apoB-retentive molecules in prelesional susceptible versus prelesional resistant sites remains an important area for study M