Smith Jonathan D
Cleveland Clinic, Department of Cell Biology, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Curr Opin Investig Drugs. 2010 Sep;11(9):989-96.
Although statin treatment leads consistently to a reduction in major adverse coronary events and death in clinical trials, approximately 60 to 70% residual risk of these outcomes still remains. One frontier of investigational drug research is treatment to increase HDL, the 'good cholesterol' that is associated with a reduced risk of coronary artery disease. HDL and its major protein apolipoprotein A-I (apoAI) are protective against atherosclerosis through several mechanisms, including the ability to mediate reverse cholesterol transport. This review focuses on the preclinical and clinical findings for two types of therapies for the treatment of atherosclerosis: apoAI-containing compounds and apoAI mimetic peptides. Both of these therapies have excellent potential to be useful clinically to promote atherosclerosis regression and stabilize existing plaques, but significant hurdles must be overcome in order to develop these approaches into safe and effective therapies.
尽管在临床试验中他汀类药物治疗始终能降低主要不良冠脉事件和死亡风险,但这些结局仍有大约60%至70%的残余风险。研究性药物研发的一个前沿领域是通过治疗来提高高密度脂蛋白(HDL)水平,HDL即“好胆固醇”,与降低冠心病风险相关。HDL及其主要蛋白质载脂蛋白A-I(apoAI)通过多种机制预防动脉粥样硬化,包括介导逆向胆固醇转运的能力。本综述聚焦于两种治疗动脉粥样硬化的疗法的临床前和临床研究结果:含apoAI的化合物和apoAI模拟肽。这两种疗法在临床上都有极大潜力促进动脉粥样硬化消退并稳定现有斑块,但要将这些方法开发成安全有效的疗法,还必须克服重大障碍。