Attenuation of MicroRNA-495 Derepressed PTEN to Effectively Protect Rat Cardiomyocytes from Hypertrophy.

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.