Adameova A, Xu Y J, Duhamel T A, Tappia P S, Shan L, Dhalla N S
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Curr Pharm Des. 2009;15(27):3094-107. doi: 10.2174/138161209789058048.
The accumulation of lipids within arteries remains to be the initial impulse for the pathogenesis of atherosclerosis; however, both inflammation and oxidative stress are considered to play a critical role in this process. Several lipid lowering drugs are used as the first line therapy in atherosclerosis; however, different agents have been found to exhibit beneficial effects which are independent of their lipid lowering activity. Both statins and fibrates have been reported to exert anti-inflammatory and anti-oxidative effects in addition to their anti-atherosclerotic actions. Furthermore, anti-hypertensive, anti-diabetic and anti-platelet drugs, which reduce oxidative stress and inflammation, have been shown to attenuate atherosclerosis. In addition, novel substances such as HDL-related agents, cyclopentenone prostaglandins, lipoprotein-associated phospholipase A(2) inhibitors, 5-lipoxygenase pathway inhibitors, acyl CoA: cholesterol acyltransferase inhibitors, analogues of probucol and lysophosphatidic acid antagonists have been developed for the treatment of atherosclerosis as a consequence of their actions on oxidative stress and inflammation. The present article reviews the involvement of inflammation and oxidative stress in the pathogenesis of atherosclerosis and focuses on the mechanisms of some clinically used as well as potential anti-atherosclerotic substances with anti-inflammatory and anti-oxidative properties.
动脉内脂质的蓄积仍是动脉粥样硬化发病机制的初始诱因;然而,炎症和氧化应激在这一过程中均被认为起着关键作用。几种降脂药物被用作动脉粥样硬化的一线治疗药物;然而,已发现不同药物展现出与其降脂活性无关的有益作用。他汀类药物和贝特类药物除具有抗动脉粥样硬化作用外,均已报道具有抗炎和抗氧化作用。此外,具有降低氧化应激和炎症作用的抗高血压药、抗糖尿病药和抗血小板药已显示可减轻动脉粥样硬化。另外,诸如高密度脂蛋白相关制剂、环戊烯酮前列腺素、脂蛋白相关磷脂酶A2抑制剂、5-脂氧合酶途径抑制剂、酰基辅酶A:胆固醇酰基转移酶抑制剂、普罗布考类似物和溶血磷脂酸拮抗剂等新型物质,因其对氧化应激和炎症的作用,已被研发用于治疗动脉粥样硬化。本文综述了炎症和氧化应激在动脉粥样硬化发病机制中的作用,并着重探讨了一些临床应用的以及具有抗炎和抗氧化特性的潜在抗动脉粥样硬化物质的作用机制。