University of Chicago, Institute for Cardiovascular Research, Chicago, IL 60637, USA.
Transl Res. 2013 May;161(5):381-92. doi: 10.1016/j.trsl.2012.12.004. Epub 2012 Dec 27.
MicroRNAs are now recognized as important regulators of cardiovascular genes with critical roles in normal development and physiology, as well as disease development. MicroRNAs (miRNAs) are small noncoding RNAs approximately 22 nucleotides in length that regulate expression of target genes through sequence-specific hybridization to the 3' untranslated region of messenger RNAs and either block translation or direct degradation of their target messenger RNA. They have been shown to participate in cardiovascular disease pathogenesis including atherosclerosis, coronary artery disease, myocardial infarction, heart failure, and cardiac arrhythmias. Broadly defined, cardiac arrhythmias are a variation from the normal heart rate or rhythm. Arrhythmias are common and result in significant morbidity and mortality. Ventricular arrhythmias constitute a major cause for cardiac death, particularly sudden cardiac death in the setting of myocardial infarction and heart failure. As advances in pharmacologic, device, and ablative therapy continue to evolve, the molecular insights into the basis of arrhythmia is growing with the ambition of providing additional therapeutic options. Electrical remodeling and structural remodeling are identified mechanisms underlying arrhythmia generation; however, published studies focusing on miRNAs and cardiac conduction are sparse. Recent studies have highlighted the role of miRNAs in cardiac rhythm through regulation of key ion channels, transporters, and cellular proteins in arrhythmogenic conditions. This article aims to review the studies linking miRNAs to cardiac excitability and other processes pertinent to arrhythmia.
MicroRNAs 现已被公认为心血管基因的重要调控因子,在正常发育和生理过程以及疾病发展中起着关键作用。MicroRNAs(miRNAs)是大约 22 个核苷酸长度的小非编码 RNA,通过与信使 RNA 的 3'非翻译区的序列特异性杂交来调节靶基因的表达,从而阻止翻译或直接降解其靶信使 RNA。它们已被证明参与了包括动脉粥样硬化、冠状动脉疾病、心肌梗死、心力衰竭和心律失常在内的心血管疾病的发病机制。广义上讲,心律失常是指心率或节律的正常变化。心律失常很常见,会导致显著的发病率和死亡率。室性心律失常是导致心脏死亡的主要原因,特别是在心肌梗死和心力衰竭的情况下发生的心脏性猝死。随着药物、器械和消融治疗的不断进步,心律失常基础的分子认识也在不断发展,以期提供更多的治疗选择。电重构和结构重构是心律失常发生的潜在机制;然而,针对 miRNAs 和心脏传导的已发表研究却很少。最近的研究强调了 miRNAs 通过调节心律失常条件下的关键离子通道、转运体和细胞蛋白在心脏节律中的作用。本文旨在综述与 miRNAs 调节心脏兴奋性以及与心律失常相关的其他过程的相关研究。