Role of eukaryotic translation initiation factors 3a in hypoxia-induced right ventricular remodeling of rats

Aim: Eukaryotic translation initiation factors 3a (eIF3a) is involved in regulating cell cycle, cell division, growth and differentiation. Previous studies suggest a role of eIF3a on fibrosis disease and cellular proliferation and differentiation of fibroblasts. The present study aims to investigate the role of eIF3a on hypoxia-induced right ventricular (RV) remodeling and underlying mechanism. Main methods: RV remodeling was induced by hypoxia (10% O-2, 3 weeks) in rats. Primary cardiac fibroblasts were cultured in vitro and their proliferation was investigated by MTS and EdU incorporation method. eIF3a knockdown was conducted by eIF3a siRNA. The expression/level of TGF-beta 1, eIF3a, p27 and alpha-SMA, collagen-I, collagen-III, ANP and BNP were analyzed by ELISA, real-time PCR or Western blot. Key findings: The expression of eIF3a was obviously increased in right ventricle of RV remodeling rats accompanied by up-regulation of alpha-SMA and collagens. In cultured cardiac fibroblasts, application of exogenous TGF-beta 1-induced cellular proliferation and differentiation concomitantly with up-regulation of eIF3a expression and down-regulation of p27 expression. The effects of TGF-beta 1-induced proliferation and up-regulation of alpha-SMA and collagen in cardiac fibroblasts were abolished by eIF3a siRNA. eIF3a siRNA reversed TGF-beta 1 induced down-regulation of p27 expression. Significance: The eIF3a plays a crucial role in hypoxia-induced RV remodeling by regulating TGF-beta 1-induced proliferation and differentiation of cardiac fibroblasts, which is mediated via eIF3a/p27 pathway. (C) 2015 Elsevier Inc. All rights reserved.