Trimetazidine improves right ventricular function by increasing miR-21 expression

Liu,Fang; Yin,Li; Zhang,Lulu; Liu,Wenhua; Liu,Jingjin; Wang,Yongshun; Yu,Bo

doi:10.3892/ijmm.2012.1078

Trimetazidine improves right ventricular function by increasing miR-21 expression

Authors:
- Fang Liu
- Li Yin
- Lulu Zhang
- Wenhua Liu
- Jingjin Liu
- Yongshun Wang
- Bo Yu
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Affiliations: Key Laboratories of Education Ministry for Myocardial Ischemia Mechanism and Treatment, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China, Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China
Published online on: July 25, 2012 https://doi.org/10.3892/ijmm.2012.1078
Pages: 849-855

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Abstract

Trimetazidine (TMZ) improves left ventricular (LV) function and alleviates angina. TMZ is a metabolism-related drug, but its molecular actions and non-metabolic effects have not yet been elucidated. In this study, we investigated whether TMZ improves right ventricular (RV) function and decreases apoptosis in RV myocardial cells (RVMCs) by regulating miRNA-21 (miR-21) expression in vitro and in vivo. We used cultivated RVMCs and LV myocardial cells (LVMCs) and provided hypoxic stimulation for 24 h to induce MC apoptosis. RVMCs showed more severe apoptosis as indicated by terminal deoxynucleotidyl-transferase-mediated dUTP nick end-labeling (TUNEL) staining and caspase-3 protein and activity assays. The decrease in miR-21 expression was more dramatic in RVMCs. Subsequently, TMZ (10 µM) was added to the RVMCs prior to hypoxic stimulation. The TMZ-treated RVMCs showed less apoptosis and an increased expression of miR-21. The transfection of RVMCs with a miR‑21-specific inhibitor weakened the protective effects of TMZ. To evaluate TMZ effectiveness in right heart failure, we used a combination treatment of hypoxia and the vascular endothelial growth factor receptor blocker, Su5416, to construct a stable model, and administered TMZ. TMZ improved RV function (as indicated by an increase in tricuspid annular plane systolic excursion), and inhibited fibrosis. TMZ also protects RVMCs againts apoptosis and increases miR-21 expression.

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