Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, 10 Amistad St., New Haven, CT 06510. USA.
Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, 10 Amistad St., New Haven, CT 06510. USA.
Vascul Pharmacol. 2019 Mar;114:93-102. doi: 10.1016/j.vph.2018.06.011. Epub 2018 Jun 19.
Cardiovascular disease (CVD), the leading cause of death and morbidity in the Western world, begins with lipid accumulation in the arterial wall, which is the initial step in atherogenesis. Alterations in lipid metabolism result in increased risk of cardiometabolic disorders, and treatment of lipid disorders remains the most common strategy aimed at reducing the incidence of CVD. Work done over the past decade has identified numerous classes of non-coding RNA molecules including microRNAs (miRNAs) and long-non-coding RNAs (lncRNAs) as critical regulators of gene expression involved in lipid metabolism and CVD, mostly acting at post-transcriptional level. A number of miRNAs, including miR-33, miR-122 and miR-148a, have been demonstrated to play important role in controlling the risk of CVD through regulation of cholesterol homeostasis and lipoprotein metabolism. lncRNAs are recently emerging as important regulators of lipid and lipoprotein metabolism. However, much additional work will be required to fully understand the impact of lncRNAs on CVD and lipid metabolism, due to the high abundance of lncRNAs and the poor-genetic conservation between species. This article reviews the role of miRNAs and lncRNAs in lipid and lipoprotein metabolism and their potential implications for the treatment of CVD.
心血管疾病(CVD)是西方世界死亡和发病的主要原因,始于动脉壁中的脂质积累,这是动脉粥样硬化形成的初始步骤。脂质代谢的改变导致患心脏代谢疾病的风险增加,而治疗脂质紊乱仍然是降低 CVD 发病率的最常见策略。过去十年的研究工作已经确定了许多非编码 RNA 分子类别,包括 microRNAs(miRNAs)和长非编码 RNA(lncRNAs),它们是参与脂质代谢和 CVD 的基因表达的关键调节剂,主要在转录后水平发挥作用。许多 miRNAs,包括 miR-33、miR-122 和 miR-148a,已被证明通过调节胆固醇稳态和脂蛋白代谢在控制 CVD 风险方面发挥重要作用。lncRNAs 最近作为脂质和脂蛋白代谢的重要调节剂而出现。然而,由于 lncRNAs 的高丰度和物种间遗传保守性差,需要进行更多的工作才能充分了解 lncRNAs 对 CVD 和脂质代谢的影响。本文综述了 miRNAs 和 lncRNAs 在脂质和脂蛋白代谢中的作用及其在 CVD 治疗中的潜在意义。