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Int J Med Sci 2012; 9(6):413-423. doi:10.7150/ijms.4514 This issue Cite

Research Paper

MicroRNA 21 Inhibits Left Ventricular Remodeling in the Early Phase of Rat Model with Ischemia-reperfusion Injury by Suppressing Cell Apoptosis

Yanjun Qin¹, Yueqing Yu², Hua Dong¹, Xiaohua Bian¹, Xuan Guo¹, Shimin Dong^{1 ✉}

1. Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang 050051, China;
2. Department of Clinical Laboratory, the General Hospital of Hebei Province, Shijiazhuang 050051, China.

✉ Corresponding author: Shimin Dong, Department of Emergency, the third hospital of Hebei Medical University, Shijiazhuang 050051, China. Tel: 0086-311-88602230; E-mail: lvguangwedu.cn.

Abstract

Objective: To determine the role of microRNA 21(miR-21) on left ventricular remodeling of rat heart with ischemia-reperfusion (I/R) injury and to investigate the underlying mechanism of miR-21 mediated myocardium protection.

Methods: Rats were randomly divided into three groups: an I/R model group with Ad-GFP (Ad-GFP group), an I/R model group with Ad-miR-21 (Ad-miR-21 group) and a sham-surgery group. Changes in hemodynamic parameters were recorded at 1 week after I/R. Histological diagnosis was achieved by hematoxylin and eosin (H&E). Left ventricular (LV) dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells were measured. Primary cultures of neonatal rat cardiac ventricular myocytes were performed and cell ischemic injury was induced by hypoxia in a serum- and glucose-free medium, and reoxygenation (H/R).MiR-21 inhibitor and pre-miR-21 were respectively added to the culture medium for the miR-21 knockdown and for the miR-21 up-regulation. qRT-PCR was used to determine the miR-21 levels in cultured cells. Flow cytometry was performed to examine the cell apoptosis.

Results: In the Ad-miR-21 group, LV dimensions, myocardial infarct size, LV/BW, collagen type Ⅰ, type Ⅲ and PCNA positive cells all significantly decreased compared with the Ad-GFP group. At 1 week after I/R, the Ad-miR-21 significantly improved LVSP, LV +dp/dt_max, LV − dp/dt_min, and decreased heart rate (HR) and LVEDP compared with the Ad-GFP group. Compared with the Ad-GFP, the cell apoptotic rate significantly decreased in the Ad-miR-21 group. The miR-21 inhibitor exacerbated cardiac myocyte apoptosis and the pre-miR-21 decreased hypoxia/reoxygenation- induced cardiac myocyte apoptosis.

Conclusions: Ad-miR-21 improves LV remodeling and decreases the apoptosis of myocardial cells, suggesting the possible mechanism by which Ad-miR-21 functions in protecting against I/R injury.

Keywords: microRNA 21, ischemia-reperfusion, ventricular remodeling, hemodynamic, collagen, apoptosis, rat.

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