Feig Jonathan E, Feig Jessica L, Dangas George D
aDepartment of Medicine/Cardiology, Heart and Vascular Institute, Johns Hopkins Hospital, Baltimore, Maryland bDepartment of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital cThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai dCardiovascular Research Foundation, New York, New York, USA.
Coron Artery Dis. 2016 Nov;27(7):592-603. doi: 10.1097/MCA.0000000000000408.
On the basis of studies that extend back to the early 1900s, regression and stabilization of atherosclerosis in humans has progressed from being a concept to one that is achievable. Successful attempts at regression generally applied robust measures to improve plasma lipoprotein profiles. Possible mechanisms responsible for lesion shrinkage include decreased retention of atherogenic apolipoprotein B within the arterial wall, efflux of cholesterol and other toxic lipids from plaques, emigration of lesional foam cells out of the arterial wall, and influx of healthy phagocytes that remove necrotic debris as well as other components of the plaque. Currently available clinical agents, however, still fail to stop most cardiovascular events. For years, HDL has been considered the 'good cholesterol.' Clinical intervention studies to causally link plasma HDL-C levels to decreased progression or to the regression of atherosclerotic plaques are relatively few because of the lack of therapeutic agents that can selectively and potently increase HDL-C. The negative results of studies that were carried out have led to uncertainty as to the role that HDL plays in atherosclerosis. It is becoming clearer, however, that HDL function rather than quantity is most crucial and, therefore, discovery of agents that enhance the quality of HDL should be the goal.
基于可追溯到20世纪初的研究，人类动脉粥样硬化的消退和稳定已从一个概念发展成为一种可实现的状态。成功的消退尝试通常采用强有力的措施来改善血浆脂蛋白谱。导致病变缩小的可能机制包括动脉壁内致动脉粥样硬化载脂蛋白B的潴留减少、胆固醇和其他有毒脂质从斑块中流出、病变泡沫细胞移出动脉壁以及健康吞噬细胞流入以清除坏死碎片和斑块的其他成分。然而，目前可用的临床药物仍无法阻止大多数心血管事件。多年来，高密度脂蛋白（HDL）一直被视为“好胆固醇”。由于缺乏能够选择性且有效地提高HDL-C的治疗药物，将血浆HDL-C水平与动脉粥样硬化斑块进展减缓或消退建立因果联系的临床干预研究相对较少。已开展研究的负面结果导致人们对HDL在动脉粥样硬化中所起的作用存在不确定性。然而，越来越清楚的是，HDL的功能而非数量最为关键，因此，发现能够提高HDL质量的药物应成为目标。
