Effects of miR-124 over-expression on right ventricular remodeling in rats with pulmonary hypertension |
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Authors: | ZHENG Chang-long FU Yong-mei ZHAN Hao-hong CHEN Tian-tian ZOU Yong LIANG Cai-qian |
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Affiliation: | 1. Department of Emergency, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China;2. Department of Blood Transfusion, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China |
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Abstract: | AIM: To investigate the effect of microRNA-124 (miR-124) over-expression mediated by adeno-associated virus (AAV) on right ventricular remodeling in rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). METHODS: Male SD rats (n=32) were randomly divided into 4 groups:normal control (control) group, MCT+normal saline (NS) group, MCT+AAV-GFP (MCT+GFP) group and MCT+AAV-miR-124 (MCT+miR-124) group. The rats in the latter 3 groups were instilled slowly with 100 μL NS, AAV-GFP and AAV-miR-124 by orotracheal instillation after anesthesia, respectively. Three weeks later, MCT (60 mg/kg) was intraperitoneally injected to establish the PAH model. Right ventricular systolic blood pressure (RVSP) and mean arterial pressure of the rats were measured, and right ventricular hypertrophy index (RVHI) and right ventricular weight index (RVWI) were calculated. The pathological sections of the right heart were stained with Sirius red, and the pathological changes of myocardium were observed under a microscope. The expression of miR-124 in the lung tissues was detected by RT-qPCR. The protein levels of transforming growth factor-β1(TGF-β1) and p-Smad2 in right heart tissues were determined by Western blot. RESULTS: Compared with control group, RVSP, RVHI, RVWI and the protein levels of TGF-β1 and p-Smad2 in MCT+NS group and MCT+GFP group were significantly increased (P<0.05), the right ventricular myocytes were significantly enlarged, and collagen deposition was significantly increased. However, compared with MCT+GFP group, RVSP, RVHI, RVWI and the protein levels of TGF-β1 and p-Smad2 in MCT+miR-124 group were significantly decreased (P<0.05), the degree of right ventricular myocyte hypertrophy was significantly reduced, and collagen deposition was significantly reduced. CONCLUSION: Over-expression of miR-124 obviously reduces RVSP of rats induced by MCT and relieves myocardial remodeling, which may be related to the down-regulation of TGF-β1 and p-Smad2. |
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Keywords: | Pulmonary hypertension MicroRNA-124 Monocrotaline Ventricular remodeling |
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