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[基于大型他汀类药物试验证据的动脉粥样硬化]

[Atherosclerosis in light of the evidence from large statin trials].

作者信息

Cortese C, Bernardini S, Motti C

机构信息

Dipartimento di Medicina Interna, Università degli Studi Tor Vergata di Roma.

出版信息

Ann Ital Med Int. 2000 Jan-Mar;15(1):103-7.

Abstract

The results of the large trials with the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (or statins) in terms of clinical benefits in patients with coronary artery disease indicate that these drugs act in a complex way on several pathways involved in the atherosclerotic process. Beyond their lipid-lowering activity, statins appear to modify many characteristics of the arterial wall, resulting in protection against the progression of plaque growth and/or the precipitation of acute events. The so called "pleiotropic" effects of statins, such as the restoration of endothelial activity, the antioxidant potential or the antiproliferative effect on smooth muscle cells, have been investigated mainly in in vitro experiments. In the near future, it will be necessary to unravel the biological significance and the clinical relevance of these effects, which also involve other pathological conditions such as cancer and osteoporosis. Furthermore, lessons from the trials with statins have allowed a better understanding of the mechanisms leading to atherosclerosis which is now considered as an inflammatory process affecting the vascular wall. This has opened new perspectives in the search for the development of newer and more targeted anti-atherogenic drugs.

摘要

针对3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶抑制剂(即他汀类药物)在冠状动脉疾病患者中的临床获益情况所开展的大型试验结果表明,这些药物通过多种复杂途径作用于动脉粥样硬化进程涉及的多个通路。除了其降脂活性外,他汀类药物似乎还能改变动脉壁的许多特性,从而预防斑块进展和/或急性事件的发生。他汀类药物的所谓“多效性”作用,如内皮活性的恢复、抗氧化潜力或对平滑肌细胞的抗增殖作用,主要是在体外实验中进行研究的。在不久的将来,有必要阐明这些作用的生物学意义和临床相关性,而这些作用还涉及其他病理状况,如癌症和骨质疏松症。此外,他汀类药物试验所积累的经验使人们对动脉粥样硬化的发病机制有了更好的理解,动脉粥样硬化现在被认为是一种影响血管壁 的炎症过程。这为研发更新型、更具针对性的抗动脉粥样硬化药物开辟了新的前景。

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