Department of Cell Biology, Harvard Medical School & Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.
Curr Atheroscler Rep. 2011 Jun;13(3):202-7. doi: 10.1007/s11883-011-0179-y.
Defects in homeostatic regulation of cholesterol and fatty acids are associated with major cardiometabolic risk factors that are prevalent in type 2 diabetes and atherosclerotic cardiovascular disease. Regulatory input is found at many levels; however, recent findings have revealed pivotal roles for small non-coding RNAs (microRNAs) of the endogenous RNA interference pathway in post-transcriptional control of major regulatory mechanisms underpinning cholesterol and energy homeostasis. In addition, aberrant expression of microRNAs has been implicated in marked pathophysiologic events contributing to the progression and development of atherosclerosis, including loss of endothelial integrity, vascular smooth muscle cell proliferation, neointimal hyperplasia, and foam cell formation. This review surveys the impact of microRNA-mediated regulation in biological processes governing the cholesterol/lipoprotein metabolism, fatty acid β-oxidation (eg by miR-122 and miR-33), and endothelial dysfunction related to atherosclerosis. Given the current advances in microRNA-based technologies, the clinical potential of microRNAs as novel therapeutic targets is highlighted as new alternative strategies to ameliorate cardiometabolic diseases.
胆固醇和脂肪酸的动态平衡调节缺陷与 2 型糖尿病和动脉粥样硬化性心血管疾病中普遍存在的主要心血管代谢危险因素有关。调节作用存在于许多层面;然而,最近的研究结果揭示了内源性 RNA 干扰途径的小非编码 RNA(microRNAs)在转录后控制胆固醇和能量动态平衡的主要调节机制中的关键作用。此外,microRNAs 的异常表达与导致动脉粥样硬化进展和发展的显著病理生理事件有关,包括内皮完整性丧失、血管平滑肌细胞增殖、新生内膜过度增生和泡沫细胞形成。这篇综述调查了 microRNA 介导的调节在控制胆固醇/脂蛋白代谢、脂肪酸β-氧化(例如 miR-122 和 miR-33)以及与动脉粥样硬化相关的内皮功能障碍的生物学过程中的影响。鉴于 microRNA 相关技术的当前进展,强调了 microRNAs 作为新型治疗靶点的临床潜力,为改善代谢性心血管疾病提供了新的替代策略。