State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, 20 Dongdajie, 100071 Beijing, China.
Cell Mol Life Sci. 2012 Nov;69(21):3561-70. doi: 10.1007/s00018-012-1126-y. Epub 2012 Aug 25.
Cardiac hypertrophy is an adaptive enlargement of the myocardium in response to altered stress or injury. The cellular responses of cardiomyocytes and non-cardiomyocytes to various signaling pathways should be tightly and delicately regulated to maintain cardiac homeostasis and prevent pathological cardiac hypertrophy. MicroRNAs (miRNAs) are endogenous, single-stranded, short non-coding RNAs that act as regulators of gene expression by promoting the degradation or inhibiting the translation of target mRNAs. Recent studies have revealed expression signatures of miRNAs associated with pathological cardiac hypertrophy and heart failure in humans and mouse models of heart diseases. Increasing evidence indicates that dysregulation of specific miRNAs could alter the cellular responses of cardiomyocytes and non-cardiomyocytes to specific signaling upon the pathological hemodynamic overload, leading to cardiac hypertrophy and heart failure. This review summarizes the cell-autonomous functions of cardiomyocyte miRNAs regulated by different pathways and the roles of non-cardiomyocyte miRNAs in cardiac hypertrophy. The therapeutic effects of a number of miRNAs in heart diseases are also discussed.
心肌肥厚是心肌对各种应激或损伤的适应性增大。心肌细胞和非心肌细胞对各种信号通路的细胞反应应该受到严格和精细的调节,以维持心脏的内稳态并防止病理性心肌肥厚。microRNAs(miRNAs)是内源性的、单链、短的非编码 RNA,通过促进靶 mRNA 的降解或抑制翻译来作为基因表达的调节剂。最近的研究揭示了与人类和心脏病小鼠模型中病理性心肌肥厚和心力衰竭相关的 miRNAs 的表达特征。越来越多的证据表明,特定 miRNAs 的失调可能会改变病理性血流动力学过载时心肌细胞和非心肌细胞对特定信号的细胞反应,导致心肌肥厚和心力衰竭。本综述总结了不同通路调节的心肌细胞 miRNAs 的细胞自主功能和非心肌细胞 miRNAs 在心肌肥厚中的作用。还讨论了许多 miRNA 在心脏病中的治疗效果。