MicroRNA-328 as a regulator of cardiac hypertrophy.

International journal of cardiology 2014 May 1

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Cardiac hypertrophy is a primary predictor of progressive heart disease that often results in heart failure. Growing evidence has demonstrated that microRNAs (miRNAs) play a critical role in regulating cardiac hypertrophy. This study was designed to evaluate the effect of miR-328 on cardiac hypertrophy and the potential molecular mechanisms. We found that transgenic overexpression of miR-328 in the heart induced cardiac hypertrophy in mice, which was accompanied by reduced SERCA2a level increased intracellular calcium concentration and calcineurin protein level, and enhanced NFATc3 nuclear translocation. However, normalization of miR-328 level by its antisense chemically modified with locked nucleic acid (LNA-antimiR-328) reversed the changes. Forced expression of miR-328 resulted in cardiomyocyte hypertrophy in cultured neonatal rat ventricular cells, which was accompanied by downregulation of SERCA2a expression and activation of the calcineurin/NFATc3 signaling pathway. These changes were abolished by LNA-antimiR-328. We validated the SERCA2a as a direct target for miR-328. MiR-328 expression was upregulated in cardiomyocyte treated with isoproterenol (ISO) to induce hypertrophy; while knockdown of miR-328 attenuated the hypertrophic responses. The level of miR-328 was significantly elevated in a mouse model of hypertrophy by thoracic aortic banding (TAC). Consistently, SERCA2a was downregulated, whereas calcineurin were upregulated, and NFATc3 nuclear translocation was enhanced. In contrast, hypertrophy in these mice was significantly alleviated when treated with miR-328 antisense. MiR-328 promotes cardiac hypertrophy by targeting SERCA2a. Our study therefore uncovered a novel molecular mechanism for cardiac hypertrophy and indicated miR-328 as a potential therapeutic target for this cardiac condition. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Citation

Cui Li, Xuelian Li, Xu Gao, Ruixue Zhang, Ying Zhang, Haihai Liang, Chaoqian Xu, Weijie Du, Yong Zhang, Xue Liu, Ning Ma, Zhidan Xu, Leimin Wang, Xu Chen, Yanjie Lu, Jiaming Ju, Baofeng Yang, Hongli Shan. MicroRNA-328 as a regulator of cardiac hypertrophy. International journal of cardiology. 2014 May 1;173(2):268-76