Upregulating MicroRNA-203 Alleviates Myocardial Remodeling... : Journal of Cardiovascular Pharmacology (original) (raw)

Original Article

Upregulating MicroRNA-203 Alleviates Myocardial Remodeling and Cell Apoptosis Through Downregulating Protein Tyrosine Phosphatase 1B in Rats With Myocardial Infarction

Zhang, Jing MD*; Pan, Jianyuan MS*; Yang, Mengsi MS*; Jin, Xiaoqin MS*; Feng, Jun MS*; Wang, Ailing MS†; Chen, Zhenfei MS*

*Department of Cardiovascular Physiology, The Second People Hospital of He Fei, Hefei City, Anhui Province, People's Republic of China; and

†Department of Cardiovascular Medicine, The First Affilated Hospital of Anhui Medical University, Hefei City, Anhui Province, People's Republic of China.

Reprints: Zhenfei Chen, MD, Department of Cardiovascular, The Second People Hospital of He Fei, No. 246 Heping Stt, Hefei City, Anhui Province 230021, People's Republic of China (e-mail: [email protected]).

The authors report no conflicts of interest.

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

Abstract

Myocardial infarction (MI) is one of cardiovascular diseases with high incidence and mortality. MicroRNAs, as posttranscriptional regulators of genes, are involved in many diseases, including cardiovascular diseases. The aim of the present study was to determine whether miR-203 was functional in MI therapy and how it worked. Left anterior descending artery ligation and hypoxia/reoxygenation (H/R) treatment were, respectively, performed to obtain MI rats and hypoxia-injured H9c2 cells. Western blot and quantitative real-time polymerase chain reaction were used to determine protein levels and messenger RNA of relevant genes, respectively. Lentivirus-mediated overexpression of miR-203 was performed to study the miR-203 functions on left ventricular remodeling, infarct size, and cardiomyocyte apoptosis. Compared with the sham group, miR-203 levels were significantly decreased in MI and H/R groups. However, overexpressing miR-203 greatly improved the cardiac function, reduced infarct size in rats after MI and weakened infarction-induced apoptosis by increasing Bcl-2 and reducing decreasing Bax, cleaved caspase-3, and cleaved caspase-9. In addition, Protein tyrosine phosphatase 1B (PTP1B) was proved as a target of miR-203 in cardiomyocytes, and it was negatively regulated by miR-203. Further experiments indicated that PTP1B overexpression could remarkably inhibit miR-203-mediated antiapoptosis of cardiomyocytes and alleviate protective effects of miR-203 on mitochondria after H/R treatment. Altogether, miR-203 prevented infarction-induced apoptosis by regulating PTP1B, including reducing proapoptosis proteins, inactivating caspase pathway, and protecting mitochondria. In conclusion, miR-203 had abilities to alleviate MI-caused injury on myocardium tissues and reduce mitochondria-mediated apoptosis, which might be a potential target used for MI therapy.