Jie Fu1, Yiwei Chen1, Fen Li1,2. 1. Department of Cardiology, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China. 2. Shanghai Pediatric Congenital Heart Disease Institute, Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Abstract
BACKGROUND: The effect of microRNA (miR)-495 on cardiomyocyte hypertrophy was explored by investigating the expression of proteins in the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway. METHODS: The study used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) administration (60 mg/kg) for 2 weeks. Arterial wall thickness and right ventricular hypertrophy were examined by hematoxylin and eosin (HE) staining in the lungs and hearts. The expression level of miR-495 and PTEN was analyzed by quantitative (q)PCR and Western blotting. From the cellular level, we used loss-of-function approaches to investigate the functional roles of miR-495 in cardiac hypertrophy induced by angiotensin II (Ang II) with immunofluorescence, qPCR, and Western blotting. RESULTS: The results showed that upregulation of miR-495 markedly influenced the expression of hypertrophic markers, including the induction of nppa and the inhibition of myh6. In contrast, a reduction in the level of miR-495 attenuated an Ang II-induced hypertrophic reaction. Furthermore, PTEN was identified as a potential target of miR-495 by a bioinformatics algorithm. Luciferase analysis and Western blot analysis confirmed that the contribution of miR-495 to cardiomyocyte hypertrophy may partly be through targeting PTEN. CONCLUSIONS: Attenuation of miR-495 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy.
BACKGROUND: The effect of microRNA (miR)-495 on cardiomyocyte hypertrophy was explored by investigating the expression of proteins in the phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway. METHODS: The study used a rat model of pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT) administration (60 mg/kg) for 2 weeks. Arterial wall thickness and right ventricular hypertrophy were examined by hematoxylin and eosin (HE) staining in the lungs and hearts. The expression level of miR-495 and PTEN was analyzed by quantitative (q)PCR and Western blotting. From the cellular level, we used loss-of-function approaches to investigate the functional roles of miR-495 in cardiac hypertrophy induced by angiotensin II (Ang II) with immunofluorescence, qPCR, and Western blotting. RESULTS: The results showed that upregulation of miR-495 markedly influenced the expression of hypertrophic markers, including the induction of nppa and the inhibition of myh6. In contrast, a reduction in the level of miR-495 attenuated an Ang II-induced hypertrophic reaction. Furthermore, PTEN was identified as a potential target of miR-495 by a bioinformatics algorithm. Luciferase analysis and Western blot analysis confirmed that the contribution of miR-495 to cardiomyocyte hypertrophy may partly be through targeting PTEN. CONCLUSIONS: Attenuation of miR-495 derepressed PTEN to effectively protect rat cardiomyocytes from hypertrophy.
Authors: Teng Li; Yuanyuan Zhong; Tao Tang; Jiekun Luo; Hanjin Cui; Rong Fan; Yang Wang; Dongsheng Wang Journal: Drug Des Devel Ther Date: 2018-11-01 Impact factor: 4.162