miRNA expression in the failing human heart: Functional correlates
miRNA expression in the failing human heart: Functional correlates
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DOI：
10.1016/j.yjmcc.2008.04.014
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发表时间：
2008-08-01
影响因子：
5
通讯作者：
Port, J. David
中科院分区：
文献类型：
--
作者：
Sucharov, Carmen;Bristow, Michael R.;Port, J. David
MicroRNAs （miRNAs）是一种小的、非编码的、类似于22个核苷酸的调控rna，是基因表达程序的关键调控因子。它们在心血管系统中的作用直到最近才开始被探索；然而，mirna表达的变化与心脏发育以及包括心肌肥大和心力衰竭在内的几种病理生理状态有关。我们证明miRNA表达模式在两种类型的心力衰竭中是不同的：特发性扩张型心肌病和缺血性心肌病。为了观察单个mirna表达水平的变化是否与功能相关，我们在新生大鼠心肌细胞原代培养中表达了miR-92、miR-100和miR-133b的microRNA模拟物和抑制物。这些研究表明，miR-100的过表达参与了β -肾上腺素能受体介导的“成人”心脏基因（即α -肌球蛋白重链，SERCA2a）的抑制，并且miR-133b的过表达阻止了β -肾上腺素能受体刺激介导的基因表达模式的改变。综上所述，一些miRNA表达模式似乎是心肌病病因所特有的，mirs100和133b表达水平的变化有助于调节胎儿基因程序。很可能这种mir引导的关键重塑基因重编程参与了常见人类心肌病的建立和进展。(C) 2008爱思唯尔公司版权所有。
MicroRNAs (miRNAs) arc small, noncoding similar to 22-nucleotide regulatory RNAs that are key regulators of gene expression programs. Their role in the context of the cardiovascular system has only recently begun to be explored; however, changes in the expression of miRNAs have been associated with cardiac development and with several pathophysiological states including myocardial hypertrophy and heart failure. We demonstrate that miRNA expression patterns are distinct in two types of heart failure: idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. To pursue the observation that changes in expression levels of individual miRNAs are functionally relevant, microRNA mimics and inhibitors to miR-92, miR-100 and miR-133b were expressed in primary cultures of neonatal rat cardiac myocytes. These studies demonstrated that over-expression of miR-100 is involved in the beta-adrenergic receptor-mediated repression of "adult" cardiac genes (i.e., alpha-myosin heavy chain, SERCA2a), and that over-expression or miR-133b prevents changes in gene expression patterns mediated by beta-adrenergic receptor stimulation. In conclusion, some miRNA expression patterns appear to be unique to the etiology of cardiomyopathy and changes in the expression level of miRs 100 and 133b contribute to regulation of the fetal gene program. It is likely that this miR-directed reprogramming of key remodeling genes is involved in the establishment and progression of common human cardiomyopathies. (C) 2008 Elsevier Inc. All rights reserved.