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胆固醇:好坏丑——血脂异常治疗的靶点

Cholesterol: the good, the bad, and the ugly - therapeutic targets for the treatment of dyslipidemia.

作者信息

Elshourbagy Nabil A, Meyers Harold V, Abdel-Meguid Sherin S

机构信息

Shifa Biomedical Corporation, Malvern, Pa., USA.

出版信息

Med Princ Pract. 2014;23(2):99-111. doi: 10.1159/000356856. Epub 2013 Dec 11.

Abstract

Maintaining cholesterol and triglyceride (TG) levels within healthy limits is critical for decreasing the risk of heart disease. Dyslipidemia refers to the abnormal levels of lipids in the blood, including low high-density lipoprotein cholesterol (HDL-C), also known as good cholesterol, high low-density lipoprotein cholesterol (LDL-C), also known as bad cholesterol, and/or high TG levels that contribute to the development and progression of atherosclerosis. In this article we reviewed some of the current therapeutic targets for the treatment of dyslipidemia, with a primary focus on endothelial lipase and lecithin cholesterol acyl transferase for raising HDL-C, and the proprotein convertase subtilisin-like kexin type 9 (PCSK9), microsomal triglyceride transfer protein, and the messenger RNA of apolipoprotein B for lowering LDL-C. In addition, we reviewed the role of apolipoprotein AI (apoAI) in raising HDL-C, where we discuss three apoAI-based drugs under development. These are its mutated dimer (apoAI-Milano), a complex with phospholipids, and a mimetic peptide. Atherosclerosis, mainly because of dyslipidemia, is a leading cause of cardiovascular disease. Regarding the title of this article, the 'good' refers to HDL-C, the 'bad' refers to LDL-C, and the 'ugly' refers to atherosclerosis.

摘要

将胆固醇和甘油三酯(TG)水平维持在健康范围内对于降低心脏病风险至关重要。血脂异常是指血液中脂质水平异常,包括低高密度脂蛋白胆固醇(HDL-C,也称为好胆固醇)、高低密度脂蛋白胆固醇(LDL-C,也称为坏胆固醇),和/或导致动脉粥样硬化发生和发展的高TG水平。在本文中,我们综述了当前治疗血脂异常的一些治疗靶点,主要关注内皮脂肪酶和卵磷脂胆固醇酰基转移酶以升高HDL-C,以及前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(PCSK9)、微粒体甘油三酯转移蛋白和载脂蛋白B信使核糖核酸以降低LDL-C。此外,我们还综述了载脂蛋白AI(apoAI)在升高HDL-C方面的作用,讨论了三种正在研发的基于apoAI的药物。它们分别是其突变二聚体(apoAI-米兰)、与磷脂的复合物和模拟肽。动脉粥样硬化主要由血脂异常引起,是心血管疾病的主要原因。关于本文的标题,“好”指HDL-C,“坏”指LDL-C,“丑”指动脉粥样硬化。

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