Tabas I
Department of Medicine and Anatomy, Columbia University, New York, New York 10032, USA.
Annu Rev Nutr. 1999;19:123-39. doi: 10.1146/annurev.nutr.19.1.123.
The key initiating event in atherosclerosis is the retention of plasma lipoproteins in the subendothelial matrix. Subsequently, a series of biological responses to this retained material leads to specific molecular and cellular processes that promote lesion formation. There is considerable evidence that many of these biological responses, notably macrophage cholesteryl ester loading (foam cell formation), require subendothelial modification of the retained lipoproteins. Oxidation of lipoproteins is one such modification that likely occurs in vivo and promotes certain atherogenic events, but oxidation cannot explain all aspects of atherogenesis, including certain elements of macrophage foam cell formation. For this reason, there has been renewed interest in other modifications of lipoproteins that may be important in atherogenesis. This review addresses five such lipoprotein modifications, namely aggregation, glycation, immune complex formation, proteoglycan complex formation, and conversion to cholesterol-rich liposomes. The focus is on the evidence that these modifications occur in atherosclerotic lesions and on the potential role of these modified lipoproteins in atherogenesis, with an emphasis on macrophage foam cell formation.
动脉粥样硬化的关键起始事件是血浆脂蛋白在内皮下基质中的潴留。随后，针对这种潴留物质的一系列生物学反应会引发特定的分子和细胞过程，从而促进病变形成。有大量证据表明，许多此类生物学反应，尤其是巨噬细胞胆固醇酯蓄积（泡沫细胞形成），需要对潴留的脂蛋白进行内皮下修饰。脂蛋白氧化就是一种可能在体内发生并促进某些致动脉粥样硬化事件的修饰，但氧化并不能解释动脉粥样硬化的所有方面，包括巨噬细胞泡沫细胞形成的某些要素。因此，人们重新关注其他可能在动脉粥样硬化中起重要作用的脂蛋白修饰。本综述探讨了五种此类脂蛋白修饰，即聚集、糖基化、免疫复合物形成、蛋白聚糖复合物形成以及转化为富含胆固醇的脂质体。重点在于这些修饰发生在动脉粥样硬化病变中的证据以及这些修饰后的脂蛋白在动脉粥样硬化发生中的潜在作用，尤其着重于巨噬细胞泡沫细胞形成。
