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. 2007 Jun;170(6):1831-40.
doi: 10.2353/ajpath.2007.061170.

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

Yunhui Cheng  1 , Ruirui Ji, Junming Yue, Jian Yang, Xiaojun Liu, He Chen, David B Dean, Chunxiang Zhang
Affiliations

VSports注册入口 - MicroRNAs are aberrantly expressed in hypertrophic heart: do they play a role in cardiac hypertrophy?

"V体育官网" Yunhui Cheng et al. Am J Pathol. 2007 Jun.

Abstract

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 II 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 VSports手机版. .

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"V体育平台登录" Figures

Figure 1
Figure 1
Aortic banding induces cardiac hypertrophy in mice. A: Quantitative analysis of the ratio of HW (mg) to BW (g) (HW/BW) after aortic banding. B: Quantitative analysis of cardiac myocyte size in heart cross sections. *P < 0.05 compared with sham control.
Figure 2
Figure 2
Aberrant expression of miRNAs in mouse hypertrophic hearts. A: Time course changes of miRNAs that are highly expressed in mouse hearts and more than 30% dysregulated (down- or up-regulated) after aortic banding determined by microarray analysis. B: Confirmation of the aberrantly expressed miRNAs after aortic banding by qRT-PCR. C: Confirmation of the aberrantly expressed miRNAs after aortic banding by Northern blot. Note: miRNA levels in sham control hearts are defined as 100. *P < 0.05 compared with those in sham controls.
Figure 3
Figure 3
The effect of miR-21 inhibitor 2′OMe-miR-21 on miR-21 expression in cultured cardiac myocytes with hypertrophy. A: Transfection of miR-21 inhibitor 2′OMe-miR-21 (30 nmol/L) and control oligonucleotide (2′OMe-EGFP) (30 nmol/L) labeled with a fluorescent dye (red color) into the cultured cardiac myocytes. B: The effects of miR-21 inhibitor 2′OMe-miR-21 on the expression levels of miR-21 in cultured cardiac myocytes with hypertrophy. Note: Two controls were used in the experiment. The first control was a vehicle control (PBS), and the second control was 2′OMe-EGFP. *P < 0.05 compared with vehicle control.
Figure 4
Figure 4
The effect of miR-21 inhibitor 2′OMe-miR-21 on cardiac myocyte hypertrophy. A: Inhibition of miR-21 expression by miR-21 inhibitor 2′OMe-miR-21 (30 nmol/L). The mean MiR-21 level in vehicle-treated cells is defined as 1. B: The effect of miR-21 inhibitor 2′OMe-miR-21 on cardiac myocyte size in Ang II- or PE-treated cells. The mean myocyte size in vehicle-treated cells is defined as 1. C: The effect of miR-21 inhibitor 2′OMe-miR-21 on cardiac myocyte protein synthesis in Ang II- or PE-treated cells. The mean value of [3H]leucine incorporation in vehicle-treated cells are defined as 1. D: Representative cell pictures from different treatment groups. *P < 0.05 compared with vehicle control; #P < 0.05 compared with Ang II-treated group; P < 0.05 compared with PE-treated group.
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"VSports最新版本" References

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