Wissler R W
University of Chicago Medical Center, Department of Pathology, Illinois.
Am J Med. 1991 Jul 31;91(1B):3S-9S. doi: 10.1016/0002-9343(91)90050-8.
The major components of atherosclerotic plaque, ultimately responsible for clinical effects, are deposited lipids--mostly cholesteryl esters and cholesterol, derived largely from the lower-density lipoproteins of the blood--and proliferated, modified arterial smooth muscle cells with their synthesized connective tissue products. Advanced plaques vary widely in the proportion of the two components, but evidence indicates that lipid deposition--especially of lipoprotein elements--often occurs in the lesion-prone intimal areas of the artery prior to the buildup of smooth muscle cells. The 1980s were remarkably productive for investigators who study the pathogenesis of atherosclerosis. We now know of the many forms of lower-density lipoproteins, i.e., low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL), some of which are more likely to be associated with accelerated atherosclerosis and some of which are more likely to be influenced by diet. Among these forms of LDL and VLDL are LDL-1, beta-VLDL, and Lp(a). Work has been reported implicating various alterations of endothelial function in the permeability of the arterial endothelial barrier in the transport of these low-density, cholesterol-rich macromolecules. Of possibly greater interest is the developing evidence that such proliferation-stimulating molecules as platelet-derived growth factor (PDGF) can be produced by a number of cells likely to be involved in the progression of atherosclerotic plaque. In addition to platelets, these include activated monocytes and monocyte-derived macrophages, injured endothelial cells, and smooth muscle cells, which can undergo an autocrine conversion to PDGF synthesis--possibly stimulated by LDL from hyperlipidemic serum. Leukotrienes and other endothelium-associated regulatory molecules may also take part in the paracrine and autocrine mechanisms of stimulating smooth-muscle-cell proliferation. Additional recent developments that have led to a better understanding of atherosclerotic pathogenesis have occurred. The first is evidence of the involvement of oxidized LDL and its apolipoprotein B in atherogenesis. Research indicates that antioxidants have a suppressive effect on atherogenesis when oxidized LDL has been involved in lesion development. The data linking the development of autoimmune reactions to these oxidatively altered lipoproteins are also impressive. Further, there is increasing evidence that atherogenesis in nonhuman primates and in people in whom chronic sustained circulating immune complexes are involved is likely to be accelerated, even when few or no classic risk factors are present. These lesions appear to represent a distinct microarchitectural form of concentric and transmural atherosclerosis that is better classified as "atheroarteritis."
动脉粥样硬化斑块的主要成分最终导致临床症状，这些成分包括沉积的脂质（主要是胆固醇酯和胆固醇，大部分来源于血液中的低密度脂蛋白）以及增殖并发生改变的动脉平滑肌细胞及其合成的结缔组织产物。晚期斑块中这两种成分的比例差异很大，但有证据表明，在平滑肌细胞积聚之前，脂质沉积（尤其是脂蛋白成分的沉积）通常发生在动脉内膜易损部位。对于研究动脉粥样硬化发病机制的研究人员来说，20世纪80年代成果斐然。我们现在知道了低密度脂蛋白的多种形式，即低密度脂蛋白（LDL）和极低密度脂蛋白（VLDL），其中一些更易与动脉粥样硬化加速相关，一些则更易受饮食影响。在这些LDL和VLDL形式中，有LDL-1、β-VLDL和Lp(a)。有报道称，在内皮功能的各种改变与动脉内皮屏障在这些富含胆固醇的低密度大分子运输中的通透性之间存在关联。可能更令人感兴趣的是，越来越多的证据表明，诸如血小板衍生生长因子（PDGF）等增殖刺激分子可由一些可能参与动脉粥样硬化斑块进展的细胞产生。除了血小板外，这些细胞还包括活化的单核细胞和单核细胞衍生的巨噬细胞、受损的内皮细胞和平滑肌细胞，后者可发生自分泌转化以合成PDGF，这可能是由高脂血症血清中的LDL刺激所致。白三烯和其他与内皮相关的调节分子也可能参与刺激平滑肌细胞增殖的旁分泌和自分泌机制。最近还出现了一些有助于更好地理解动脉粥样硬化发病机制的新进展。第一个进展是有证据表明氧化型LDL及其载脂蛋白B参与动脉粥样硬化的发生。研究表明，当氧化型LDL参与病变发展时，抗氧化剂对动脉粥样硬化的发生有抑制作用。将自身免疫反应的发展与这些氧化改变的脂蛋白联系起来的数据也令人印象深刻。此外，越来越多的证据表明，即使很少或没有经典危险因素，非人类灵长类动物和患有慢性持续性循环免疫复合物的人群中，动脉粥样硬化的发生也可能会加速。这些病变似乎代表了一种独特的微观结构形式的同心性和透壁性动脉粥样硬化，更宜归类为“动脉粥样动脉炎”。
