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Expert Opin Drug Discov. 2014 Feb;9(2):119-24. doi: 10.1517/17460441.2014.871257. Epub 2013 Dec 12.
Lowering low-density lipoprotein-cholesterol (LDL-C) is an effective strategy to reduce cardiovascular risk. However, a significant residual risk remains in statin-treated patients. High-density lipoprotein cholesterol (HDL-C) is a strong, independent and inverse predictor of cardiovascular risk in many epidemiologic studies and has, therefore, emerged as a potential novel therapeutic target for addressing this substantial residual risk. Nevertheless, the failure of cholesteryl ester transfer protein (CETP) inhibitors and niacin in clinical trials has generated considerable speculation about the beneficial effects of HDL. Experimental studies have identified several HDL cardioprotective functions, including enhancement of macrophage reverse cholesterol transport and endothelial function and its antioxidant, anti-inflammatory and anti-thrombotic properties. Furthermore, HDL is highly heterogeneous and the atheroprotective functions of the different HDL subpopulations are not completely understood. Current available data indicate that increased HDL-C levels do not always correlate with enhanced HDL functions and, therefore, should not be considered a biomarker of HDL functionality. The clinical application of the novel HDL-based therapeutic approaches requires the development of validated and reproducible measures of key HDL functions.
降低低密度脂蛋白胆固醇（LDL-C）是降低心血管风险的有效策略。然而，在他汀类药物治疗的患者中仍存在显著的残余风险。在许多流行病学研究中，高密度脂蛋白胆固醇（HDL-C）是心血管风险的一个强有力的、独立的、反向预测因子，因此，它已成为解决这一巨大残余风险的潜在新的治疗靶点。然而，胆固醇酯转移蛋白（CETP）抑制剂和烟酸在临床试验中的失败引发了人们对 HDL 的有益作用的大量猜测。实验研究已经确定了几种 HDL 的心脏保护功能，包括增强巨噬细胞逆向胆固醇转运和内皮功能及其抗氧化、抗炎和抗血栓形成特性。此外，HDL 具有高度异质性，不同的 HDL 亚群的动脉保护功能尚不完全清楚。目前的可用数据表明，HDL-C 水平的升高并不总是与增强的 HDL 功能相关，因此，不应将其视为 HDL 功能的生物标志物。新型基于 HDL 的治疗方法的临床应用需要开发经过验证和可重复的关键 HDL 功能的测量方法。
