Schwartz C J, Valente A J, Sprague E A, Kelley J L, Cayatte A J, Mowery J
Department of Pathology, University of Texas Health Science Center, San Antonio 78284-7750.
Circulation. 1992 Dec;86(6 Suppl):III117-23.
Reviewed are various aspects of atherosclerotic plaque stabilization and regression in humans and experimental animals. Plaque regression is a function of the dynamic balance among initiation, progression, stabilization, and removal of plaque constituents. Pseudoregression, the result of the triad thrombolysis, age- or lesion-dependent arterial dilatation, and relaxation of vasospasm, may readily give rise to angiographic misinterpretation. Although lowering of plasma cholesterol and low density lipoprotein-cholesterol has demonstrated significant clinical benefits in a number of clinical trials, the magnitude of angiographic regressive changes is relatively small despite aggressive lipid-lowering regimens. The emerging need for alternative or complementary therapeutic interventions has been emphasized. In particular, they should be targeted to pivotal cellular or molecular mechanisms in initiation, progression, or stabilization. Potentially important therapeutic targets include the use of antioxidants or free radical scavengers such as Probucol or its analogues, butylated hydroxytoluene, tocopherols, and possibly the tocotrienols. Other therapeutic targets include intimal monocyte-macrophage recruitment, macrophage cholesterol acyltransferase inhibition, stimulation of the high density lipoprotein-mediated reverse cholesterol transport system, smooth muscle cell migration to and proliferation in the arterial intima, and intimal connective tissue synthesis. Whether the isoprenylated proteins associated with the cholesterol biosynthetic pathway will give rise to compounds regulating smooth muscle cell growth has yet to be determined. Because of the importance of thrombosis in the pathogenesis and progression of lesions, the need to develop interventional strategies targeted at endothelial cell thromboresistance and thromboregulation must assume a high priority in future research and development. Other areas of therapeutic promise include the calcium channel blockers and angiotensin converting enzyme inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
本文综述了人类和实验动物动脉粥样硬化斑块稳定及消退的各个方面。斑块消退是斑块成分起始、进展、稳定和清除之间动态平衡的函数。假消退是溶栓、年龄或病变依赖性动脉扩张以及血管痉挛缓解三联征的结果，很容易导致血管造影的错误解读。尽管在多项临床试验中降低血浆胆固醇和低密度脂蛋白胆固醇已显示出显著的临床益处，但尽管采用积极的降脂方案，血管造影显示的消退变化幅度相对较小。人们强调了对替代或补充治疗干预措施的新需求。特别是，这些措施应针对起始、进展或稳定过程中的关键细胞或分子机制。潜在的重要治疗靶点包括使用抗氧化剂或自由基清除剂，如普罗布考或其类似物、丁基化羟基甲苯、生育酚以及可能的生育三烯酚。其他治疗靶点包括内膜单核细胞-巨噬细胞募集、巨噬细胞胆固醇酰基转移酶抑制、刺激高密度脂蛋白介导的逆向胆固醇转运系统、平滑肌细胞向动脉内膜迁移和增殖以及内膜结缔组织合成。与胆固醇生物合成途径相关的异戊二烯化蛋白是否会产生调节平滑肌细胞生长的化合物尚待确定。由于血栓形成在病变发病机制和进展中的重要性，在未来的研发中，制定针对内皮细胞抗血栓形成和血栓调节的干预策略必须成为高度优先事项。其他有治疗前景的领域包括钙通道阻滞剂和血管紧张素转换酶抑制剂。（摘要截选至250字）
