MicroRNAs are aberrantly expressed in hypertrophic heart - Do they play a role in cardiac hypertrophy?
MicroRNAs are aberrantly expressed in hypertrophic heart - Do they play a role in cardiac hypertrophy?
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DOI：
10.2353/ajpath.2007.061170
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发表时间：
2007-06-01
影响因子：
6
通讯作者：
Zhang, Chunxiang
中科院分区：
文献类型：
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作者：
Cheng, Yunhui;Ji, Ruirui;Zhang, Chunxiang
MicroRNA (miRNA) 是最近发现的一类调节基因表达的内源性小非编码 RNA。尽管miRNA在心脏中高表达，但其在心脏病中的作用目前尚不清楚。使用旨在检测迄今为止鉴定的大多数哺乳动物 miRNA 的微阵列分析，我们证明 miRNA 在肥大的小鼠心脏中异常表达。在主动脉结扎后 7、14 和 21 天的小鼠心脏中进一步确定了异常 miRNA 表达的时间过程。通过 Northern blot 和/或实时聚合酶链反应进一步证实了 19 个最显着失调的 miRNA，其中 miR-21 引人注目，因为与假手术组相比，其增加了四倍多。在血管紧张素 H 或去氧肾上腺素刺激的培养的新生儿肥厚心肌细胞中也发现了上调最多的 miRNA miR-21 的类似异常表达。通过反义介导的耗竭（敲低）调节 miR-21 表达对心肌细胞肥大具有显着的负面影响。结果表明 miRNA 参与心脏肥大的形成。 miRNA可能成为涉及心脏肥大的心血管疾病的新治疗靶点，如高血压、缺血性心脏病、瓣膜疾病和内分泌紊乱。
MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate gene expression. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently unclear. Using microarray analysis designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated that miRNAs are aberrantly expressed in hypertrophic mouse hearts. The time course of the aberrant miRNA expression was further identified in mouse hearts at 7, 14, and 21 days after aortic banding. Nineteen of the most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real-time polymerase chain reaction, in which miR-21 was striking because of its more than fourfold increase when compared with the sham surgical group. Similar aberrant expression of the most up-regulated miRNA, miR-21, was also found in cultured neonatal hypertrophic cardiomyocytes stimulated by angiotensin H or phenylephrine. Modulating miR-21 expression via antisense-mediated depletion (knockdown) had a significant negative effect on cardiomyocyte hypertrophy. The results suggest that miRNAs are involved in cardiac hypertrophy formation. miRNAs might be a new therapeutic target for cardiovascular diseases involving cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders.