Aryal Binod, Singh Abhishek K, Rotllan Noemi, Price Nathan, Fernández-Hernando Carlos
Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine, and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
Curr Opin Lipidol. 2017 Jun;28(3):273-280. doi: 10.1097/MOL.0000000000000420.
Work over the past 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 LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) metabolism.
A number of miRNAs have emerged as important regulators of lipid metabolism, including miR-122 and miR-33. Work over the past 2 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 in the proximity of miRNA genes associated with abnormal levels of circulating lipids in humans. Several of these miRNAs, such as miR-148a and miR-128-1, target important proteins that regulate cellular cholesterol metabolism, including the LDL 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 noncoding RNA that controls cardiovascular homeostasis independent of its role in regulating lipid metabolism.
过去十年的研究已确定微小RNA（miRNA）在调节脂蛋白代谢及相关疾病（包括代谢综合征、肥胖症和动脉粥样硬化）中发挥重要作用。本综述总结了该领域的最新研究成果，重点阐述了miRNA在控制低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）代谢中的作用。
一些miRNA已成为脂质代谢的重要调节因子，包括miR-122和miR-33。过去两年的研究确定了miR-33的其他功能，包括对巨噬细胞活化和线粒体代谢的调节。此外，最近的研究表明，miR-33可调节血管稳态以及心脏对压力过载的适应性。除了miR-33和miR-122，近期的全基因组关联研究（GWAS）已在miRNA基因附近鉴定出与人类循环脂质水平异常相关的单核苷酸多态性。其中一些miRNA，如miR-148a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（ABCA1）。
微小RNA已成为胆固醇代谢的关键调节因子，也是治疗包括动脉粥样硬化在内的心脏代谢疾病的有前景的治疗靶点。在此，我们讨论该领域的最新研究成果，重点阐述miR-33控制脂质代谢和动脉粥样硬化发生的新机制，以及鉴定调节LDL代谢的新miRNA。最后，我们总结了最近的研究发现，这些发现确定miR-33是一种重要的非编码RNA，它在独立于调节脂质代谢作用之外控制心血管稳态。
