Stoekenbroek R M, Stroes E S, Hovingh G K
Department of Vascular Medicine, Academic Medical Center, 22660, 1100 DD, Amsterdam, The Netherlands.
Handb Exp Pharmacol. 2015;224:631-48. doi: 10.1007/978-3-319-09665-0_21.
A wealth of evidence indicates that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to the risk of cardiovascular disease (CVD). Consequently, HDL-C has been considered a target for therapy in order to reduce the residual CVD burden that remains significant, even after application of current state-of-the-art medical interventions. In recent years, however, a number of clinical trials of therapeutic strategies that increase HDL-C levels failed to show the anticipated beneficial effect on CVD outcomes. As a result, attention has begun to shift toward strategies to improve HDL functionality, rather than levels of HDL-C per se. ApoA-I, the major protein component of HDL, is considered to play an important role in many of the antiatherogenic functions of HDL, most notably reverse cholesterol transport (RCT), and several therapies have been developed to mimic apoA-I function, including administration of apoA-I, mutated variants of apoA-I, and apoA-I mimetic peptides. Based on the potential anti-inflammatory effects, apoA-I mimetics hold promise not only as anti-atherosclerotic therapy but also in other therapeutic areas.
大量证据表明，血浆高密度脂蛋白胆固醇（HDL-C）水平与心血管疾病（CVD）风险呈负相关。因此，HDL-C被视为治疗靶点，以减轻即使在应用当前最先进的医学干预措施后仍显著存在的残余CVD负担。然而，近年来，一些旨在提高HDL-C水平的治疗策略的临床试验未能显示出对CVD结局的预期有益效果。结果，注意力开始转向改善HDL功能的策略，而不是HDL-C本身的水平。载脂蛋白A-I（ApoA-I）是HDL的主要蛋白质成分，被认为在HDL的许多抗动脉粥样硬化功能中起重要作用，最显著的是逆向胆固醇转运（RCT），并且已经开发了几种疗法来模拟ApoA-I的功能，包括给予ApoA-I、ApoA-I的突变变体和ApoA-I模拟肽。基于潜在的抗炎作用，ApoA-I模拟物不仅有望作为抗动脉粥样硬化疗法，而且在其他治疗领域也有应用前景。
