Baldán Ángel, de Aguiar Vallim Thomas Q
Edward A. Doisy Department of Biochemistry & Molecular Biology, Center for Cardiovascular Research, and Liver Center, 1100 S. Grand Blvd., Saint Louis University, Saint Louis, MO 63104, United States.
Department of Medicine, Division of Cardiology, 650 Charles E. Young Drive S, A2-237 CHS, UCLA Los Angeles, Los Angeles, CA 90095, United States.
Biochim Biophys Acta. 2016 Dec;1861(12 Pt B):2053-2061. doi: 10.1016/j.bbalip.2016.01.021. Epub 2016 Feb 9.
Altered lipoprotein metabolism plays a key role during atherogenesis. For over 50years, epidemiological data have fueled the proposal that HDL-cholesterol (HDL-c) in circulation is inversely correlated to cardiovascular risk. However, the atheroprotective role of HDL is currently the focus of much debate and remains an active field of research. The emerging picture from research in the past decade suggests that HDL function, rather than HDL-c content, is important in disease. Recent developments demonstrate that miRNAs play an important role in fine-tuning the expression of key genes involved in HDL biogenesis, lipidation, and clearance, as well as in determining the amounts of HDL-c in circulation. Thus, it has been proposed that miRNAs that affect HDL metabolism might be exploited therapeutically in patients. Whether HDL-based therapies, alone or in combination with LDL-based treatments (e.g. statins), provide superior outcomes in patients has been recently questioned by human genetics studies and clinical trials. The switch in focus from "HDL-cholesterol" to "HDL function" opens a new paradigm to understand the physiology and therapeutic potential of HDL, and to find novel modulators of cardiovascular risk. In this review we summarize the current knowledge on the regulation of HDL metabolism and function by miRNAs. This article is part of a Special Issue entitled: MicroRNAs and lipid/energy metabolism and related diseases edited by Carlos Fernández-Hernando and Yajaira Suárez.
脂蛋白代谢改变在动脉粥样硬化形成过程中起关键作用。五十多年来,流行病学数据支持了循环中的高密度脂蛋白胆固醇(HDL-c)与心血管风险呈负相关的观点。然而,HDL的抗动脉粥样硬化作用目前是众多争论的焦点,仍是一个活跃的研究领域。过去十年的研究新情况表明,HDL功能而非HDL-c含量在疾病中起重要作用。最近的进展表明,微小RNA(miRNAs)在微调参与HDL生物合成、脂化和清除的关键基因表达以及确定循环中HDL-c的量方面发挥重要作用。因此,有人提出影响HDL代谢的miRNAs可能在患者治疗中得到应用。基于HDL的疗法单独或与基于LDL的治疗(如他汀类药物)联合使用是否能为患者带来更好的疗效,最近受到了人类遗传学研究和临床试验的质疑。从“HDL胆固醇”到“HDL功能”的重点转变为理解HDL的生理学和治疗潜力以及寻找心血管风险的新型调节剂开辟了新的范式。在本综述中,我们总结了目前关于miRNAs对HDL代谢和功能调节的认识。本文是由卡洛斯·费尔南德斯 - 埃尔南多(Carlos Fernández-Hernando)和亚贾伊拉·苏亚雷斯(Yajaira Suárez)编辑的名为《微小RNA与脂质/能量代谢及相关疾病》特刊的一部分。