MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy?

MiRNAs are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the human genome. Although miRNAs are highly expressed in the heart, their roles in heart diseases are currently completely unknown. Using microarray analysis, designed to detect the majority of mammalian miRNAs identified thus far, we demonstrated for the first time that miRNAs are aberrantly expressed in hypertrophic mouse hearts after aortic banding. Seven days after aortic banding, 105 of the 157 heart miRNAs were differentially expressed (p<0.01); 52 miRNAs were up‐regulated, and 53 miRNAs were down‐regulated. At 14 days after aortic banding, 70 of the 157 heart miRNAs were differentially expressed (35 up and 35 down), while 74 of the 157 heart miRNAs were differentially expressed (44 up and 30 down) at 21 days after aortic banding. The 19 most significantly dysregulated miRNAs were further confirmed by Northern blot and/or real‐time polymerase chain reaction, in which miR‐21 was striking out due to its over 4‐fold increase compared with that in 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 II (Ang II) or phenylephrine (PE). 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 the cardiac hypertrophy formation. MiRNAs might be a new therapeutic target for cardiovascular diseases with cardiac hypertrophy such as hypertension, ischemic heart disease, valvular diseases, and endocrine disorders.

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