Pauley Heart Center, Department of Internal Medicine, Division of Cardiology, Virginia Commonwealth University, Richmond, VA 23298, USA.
Oxid Med Cell Longev. 2018 Aug 23;2018:6141902. doi: 10.1155/2018/6141902. eCollection 2018.
Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.
机械论/哺乳动物雷帕霉素靶蛋白（mTOR）是一种非典型丝氨酸/苏氨酸激酶，属于磷酸肌醇 3-激酶（PI3K）相关激酶家族，在多种细胞过程中发挥重要作用，包括细胞生长、增殖、存活、蛋白质合成、自噬和代谢。在心血管系统中，mTOR 信号通路整合了细胞内和细胞外信号，是生理和病理过程的中央调节剂。微小 RNA（miRs）是一类短的非编码 RNA，是一种新兴的复杂的转录后调节因子，对广泛组织（包括心血管系统）的发育和稳态维持的关键基因表达具有重要作用。在过去的十年中，大量研究揭示了 miRNA 和 mTOR 信号通路在心肌梗死、肥大、纤维化、心力衰竭、心律失常、炎症和动脉粥样硬化等不同心血管病理生理学中的相互作用。在这篇综述中，我们全面介绍了 mTOR 信号通路与 miRNA 之间相互作用的机制。我们还强调了 mTOR 靶向治疗在临床试验中的最新进展，以及利用 mTOR 靶向 miR 治疗心血管疾病的新视角。
