Paumelle Réjane, Staels Bart
INSERM U545, Institut Pasteur de Lille, Boulevard du Pr. Jules Leclerc, Lille, France.
Trends Cardiovasc Med. 2008 Apr;18(3):73-8. doi: 10.1016/j.tcm.2008.01.001.
Although a change in lifestyle is the first choice in controlling cardiovascular risk, lipid-lowering drugs are effective in normalizing different forms of atherogenic dyslipidemia. Although statins are a class of drugs which primarily lower low-density lipoprotein cholesterol, fibrates decrease triglycerides, normalize the low-density lipoprotein cholesterol profile, and increase high-density lipoprotein cholesterol. As lipids are important determinants for cardiovascular diseases, these drugs reduce cardiovascular morbidity. However, a number of recent studies indicate that, in addition to their lipid-normalizing activities, statins and fibrates exhibit pleiotropic actions, such as inhibit inflammation, improve endothelial function, suppress the production of reactive oxygen species, etc. Statins are competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme of cholesterol synthesis, whereas fibrates are activators of the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha). The similarity between the pleiotropic effects of statins and fibrates is remarkable and suggests a mechanistic link between these two classes of drugs. Here we discuss recent data on the cross-talk between statins and PPARalpha agonists and the mechanisms behind these actions.
尽管改变生活方式是控制心血管风险的首选，但降脂药物在使不同形式的致动脉粥样硬化血脂异常正常化方面是有效的。虽然他汀类药物是一类主要降低低密度脂蛋白胆固醇的药物，但贝特类药物可降低甘油三酯，使低密度脂蛋白胆固醇水平正常化，并提高高密度脂蛋白胆固醇水平。由于脂质是心血管疾病的重要决定因素，这些药物可降低心血管发病率。然而，最近的一些研究表明，除了其血脂正常化活性外，他汀类药物和贝特类药物还表现出多效性作用，如抑制炎症、改善内皮功能、抑制活性氧的产生等。他汀类药物是3-羟基-3-甲基戊二酰辅酶A还原酶的竞争性抑制剂，该酶是胆固醇合成的限速酶，而贝特类药物是核受体过氧化物酶体增殖物激活受体α（PPARα）的激活剂。他汀类药物和贝特类药物多效性作用之间的相似性很显著，这表明这两类药物之间存在机制联系。在此，我们讨论关于他汀类药物和PPARα激动剂之间相互作用的最新数据以及这些作用背后的机制。
