Zakiev Emile, Feng Ma, Sukhorukov Vasily, Kontush Anatol
Laboratory of Angiopathology, Institute of General Pathology and Pathophysiology, 125315 Moscow. Russian Federation.
INSERM UMR_S 1166, Faculte de Medecine Pitie-Salpetriere, Bld de L'Hopital 91, 75013 Paris, France; University of Pierre and Marie Curie - Paris 6, Paris. France.
Curr Pharm Des. 2017;23(8):1207-1215. doi: 10.2174/1381612822666161027153140.
Large-scale epidemiological studies firmly established the association between low plasma levels of high-density lipoprotein-cholesterol (HDL-C) and elevated risk of cardiovascular disease. This relationship is thought to reflect the key biological function of HDL, which involves reverse cholesterol transport from the arterial wall to the liver for further excretion from the body. Other aspects of the cardioprotective HDL functionality include antioxidative, anti-inflammatory, anti-apoptotic, anti-thrombotic, vasodilatory, anti-infectious and antidiabetic activities. Over the last decades, wide interest in HDL as an athero- and cardioprotective particle has resulted in the development of HDL-C raising as a therapeutic approach to reduce cardiovascular risk. Several strategies to increase circulating HDL-C concentrations were developed that primarily included use of niacin and fibrates as potent HDL-C raising agents. In the statin era, inhibition of cholesteryl ester transfer protein, infusion of artificially reconstituted HDL and administration of apolipoprotein A-I mimetics were established as novel approaches to raise HDL-C. More recently, other strategies targeting HDL metabolism, such as upregulation of apolipoprotein A-I production by the liver, were added to the list of HDL therapeutics. This review summarises current knowledge of novel HDL-targeting therapies and discusses perspectives of their use.
大规模流行病学研究确凿地证实了血浆中高密度脂蛋白胆固醇（HDL-C）水平低下与心血管疾病风险升高之间的关联。这种关系被认为反映了HDL的关键生物学功能，即参与将胆固醇从动脉壁逆向转运至肝脏以便进一步从体内排出。具有心脏保护作用的HDL功能的其他方面包括抗氧化、抗炎、抗凋亡、抗血栓形成、血管舒张、抗感染和抗糖尿病活性。在过去几十年中，人们对HDL作为一种抗动脉粥样硬化和具有心脏保护作用的微粒产生了广泛兴趣，从而促使将升高HDL-C作为降低心血管风险的一种治疗方法。人们开发了几种增加循环HDL-C浓度的策略，主要包括使用烟酸和贝特类药物作为强效升高HDL-C的药物。在他汀类药物时代，抑制胆固醇酯转运蛋白、输注人工重组HDL以及给予载脂蛋白A-I模拟物被确立为升高HDL-C的新方法。最近，其他针对HDL代谢的策略，如上调肝脏中载脂蛋白A-I的产生，也被列入HDL治疗方法之中。本综述总结了目前关于新型HDL靶向治疗的知识，并讨论了其应用前景。
