Chyu Kuang-Yuh, Shah Prediman K
Division of Cardiology, Oppenheimer Atherosclerosis Research Center, Cedars-Sinai Heart Institute, Cedars-Sinai Medical Center Los Angeles, CA, USA.
Front Pharmacol. 2015 Sep 1;6:187. doi: 10.3389/fphar.2015.00187. eCollection 2015.
The HDL hypothesis stating that simply raising HDL cholesterol (HDL-C) may produce cardiovascular benefits has been questioned recently based on several randomized clinical trials using CETP inhibitors or niacin to raise HDL-C levels. However, extensive pre-clinical data support the vascular protective effects of administration of exogenous ApoA-1 containing preβ-HDL like particles. Several small proof-of-concept clinical trials using such HDL/ApoA-1 infusion therapy have shown encouraging results but definitive proof of efficacy must await large scale clinical trials. In addition to HDL infusion therapy an alternative way to exploit beneficial cardiovascular effects of HDL/ApoA-1 is to use gene transfer. Preclinical studies have shown evidence of benefit using this approach; however clinical validation is yet lacking. This review summarizes our current knowledge of the aforementioned strategies.
高密度脂蛋白（HDL）假说认为单纯升高HDL胆固醇（HDL-C）可能会带来心血管益处，但最近基于几项使用胆固醇酯转运蛋白（CETP）抑制剂或烟酸升高HDL-C水平的随机临床试验，这一假说受到了质疑。然而，大量临床前数据支持给予含外源性载脂蛋白A-1（ApoA-1）的前β-HDL样颗粒具有血管保护作用。几项使用此类HDL/ApoA-1输注疗法的小型概念验证临床试验已显示出令人鼓舞的结果，但疗效的确切证据仍需等待大规模临床试验验证。除了HDL输注疗法外，利用HDL/ApoA-1有益心血管作用的另一种方法是基因转移。临床前研究已显示出使用这种方法有益的证据；然而，仍缺乏临床验证。本综述总结了我们目前对上述策略的认识。
