Impaired cardiac microvascular endothelial cells function induced by Coxsackievirus B3 infection and its potential role in cardiac fibrosis

CVB3 virus tropism and tissue access are modulated by cardiac microvascular endothelial cells (CMVECs) in the context of microvasculature. This study was designed to examine biological behaviors of CMVECs following CVB3 infection and its possible effects on cardiac remodeling. Data demonstrated that CVB3 increased caspase-3 activities, Bax/Bcl-2 protein ratio and TGF-β1 levels in CMVECs, accompanying with elevated microvascular permeability. Double immunofluorescence revealed co-localization of endothelial markers (CD31 and VE-cadherin) and mesenchymal markers (FSP1 and αSMA) in infected CMVECs. Western blot demonstrated that CVB3 significantly decreased the expression of endothelial markers and increased the expression of mesenchymal markers, which were reversed by SB431542 (inhibitor of TGF-β1), indicating that endothelial-to-mesenchymal transition following CVB3 infection was probably induced by CMVECs-derived TGF-β1. Excess extracellular matrix was produced by myocardial cells incubated with supernatants of infected CMVECs. Our results displayed that CVB3 induced notable biological changes of CMVECs, which may contribute to cardiac fibrosis.

► CVB3 infection in CMVECs leads to increased apoptosis, microvascular permeability and TGF-β1 production. ► CMVECs could undergo endothelial-to-mesenchymal transition after CVB3 infection. ► CVB3 infection of CMVECs is implicated in the pathogenesis of CVB3-induced cardiac fibrosis.