MicroRNAs and lipid metabolism.
MicroRNAs and lipid metabolism.
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DOI：
10.1097/mol.0000000000000420
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发表时间：
2017-06
影响因子：
4.4
通讯作者：
Fernández-Hernando C
中科院分区：
文献类型：
--
作者：
Aryal B;Singh AK;Rotllan N;Price N;Fernández-Hernando C
过去十年的工作已经确定了microRNA（miRNAS）在调节脂蛋白代谢和相关疾病（包括代谢综合征、肥胖和动脉粥样硬化）中的重要作用。本文综述了该领域的最新研究成果，强调了miRNA在控制低密度脂蛋白（LDL）和高密度脂蛋白（HDL）代谢中的作用。许多miRNA已经成为脂质代谢的重要调节因子，包括miR-122和miR-33。过去两年的工作已经确定了miR-33的其他功能，包括调节巨噬细胞活化和线粒体代谢。此外，最近已经显示，miR-33响应于压力超负荷调节血管稳态和心脏适应。除了miR-33和miR-122之外，最近的GWAS已经鉴定了与人类循环脂质异常水平相关的miRNA基因附近的单核苷酸多态性（SNP）。其中几种miRNA，如miR-148 a和miR-128-1，靶向调节细胞胆固醇代谢的重要蛋白质，包括低密度脂蛋白受体（LDLR）和ATP结合盒A1（ABCA 1）。microRNA已成为胆固醇代谢的关键调节剂，并成为治疗包括动脉粥样硬化在内的心脏代谢疾病的有前途的治疗靶点。在这里，我们讨论了该领域的最新发现，强调了miR-33控制脂质代谢和动脉粥样硬化形成的新机制，以及调节LDL代谢的新型miRNA的鉴定。最后，我们总结了最近的研究结果，确定miR-33作为一个重要的非编码RNA，控制心血管稳态独立于其在调节脂质代谢的作用。
Work over the last decade has identified the important role of microRNAs (miRNAS) in regulating lipoprotein metabolism and associated disorders including metabolic syndrome, obesity and atherosclerosis. This review summarizes the most recent findings in the field, highlighting the contribution of miRNAs in controlling low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism. A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the last two years has identified additional functions of miR-33 including the regulation of macrophage activation and mitochondrial metabolism. Moreover, it has recently been shown that miR-33 regulates vascular homeostasis and cardiac adaptation in response to pressure overload. In addition to miR-33 and miR-122, recent GWAS have identified single nucleotide polymorphisms (SNP) in the proximity of miRNAs genes associated with abnormal levels of circulating lipids in humans. Several of these miRNA, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the low-density lipoprotein receptor (LDLR) and the ATP-binding cassette A1 (ABCA1). microRNAs have emerged as critical regulators of cholesterol metabolism and promising therapeutic targets for treating cardiometabolic disorders including atherosclerosis. Here, we discuss the recent findings in the field highlighting the novel mechanisms by which miR-33 controls lipid metabolism and atherogenesis and the identification of novel miRNAs that regulate LDL metabolism. Finally, we summarize the recent findings that identified miR-33 as an important non-coding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism.