Endothelial‑to‑mesenchymal transition in human idiopathic dilated cardiomyopathy

Xie,Yeqing; Liao,Jianquan; Yu,Yong; Guo,Qi; Yang,Yingzhen; Ge,Junbo; Chen,Haozhu; Chen,Ruizhen

doi:10.3892/mmr.2017.8013

Endothelial‑to‑mesenchymal transition in human idiopathic dilated cardiomyopathy

Authors:
- Yeqing Xie
- Jianquan Liao
- Yong Yu
- Qi Guo
- Yingzhen Yang
- Junbo Ge
- Haozhu Chen
- Ruizhen Chen
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Affiliations: Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: November 8, 2017 https://doi.org/10.3892/mmr.2017.8013
Pages: 961-969
Copyright: © Xie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Dilated cardiomyopathy (DCM) is characterized by left ventricular dilation and cardiac fibrosis. Emerging evidence indicated that endothelial‑to‑mesenchymal transition (Endo‑MT) is a crucial event during organ fibrosis. This study was performed to clarify whether Endo‑MT contributed to the progression of cardiac fibrosis in DCM. Cardiac samples from patients with DCM and control were obtained. The presence of endothelial markers, cluster of differentiation (CD)31 and vascular endothelial (VE)‑cadherin, and mesenchymal markers, α smooth muscle actin (SMA) and fibroblast‑specific protein 1 (FSP1) was performed using immunohistochemistry. Co‑localization of endothelial markers and mesenchymal markers were identified using confocal immunofluorescence staining. Serum procollagen type I carboxy‑terminal propeptide (PICP) and procollagen type III amino‑terminal propeptide (PIIINP) were measured by ELISA. Protein levels of Wnt, β‑catenin and Snail were determined using western blot analysis. Immunohistochemistry and double‑immunofluorescence staining demonstrated that the expression of CD31 and VE‑cadherin were significantly decreased in DCM samples, whereas the FSP‑1, and αSMA were significantly increased. CD31 and VE‑cadherin labeling indexes were respectively negatively correlated with left ventricular end‑diastolic diameter (LVEDD) (CD31 r=‑0.82, P<0.01; VE‑cadherin r=-0.73, P<0.01), while FSP‑1 and αSMA were positively associated with LVEDD (αSMA r=0.65, P<0.01, FSP1 r=0.53, P<0.01) and left ventricular ejection fraction (αSMA r=‑0.18, P<0.05; FSP1 r=‑0.21, P<0.05). Furthermore, PICP and PIIINP levels were positively associated with the co‑expression labeling indexes (CD31/SMA co‑labeling index and PICP r=0.727, P<0.01; CD31/SMA co‑labeling index and PIIINP r=0.741, P<0.01; VE‑Cadherin/FSP‑1 co‑labeling index and PICP r=0.716, P<0.01; VE‑cadherin/FSP‑1 co‑labeling index and PIIINP r=0.648, P<0.05). Western blot analysis indicated that proteins levels of Wnt signaling and snail were significantly increased in DCM samples. These results suggested that Endo‑MT is potentially implicated in the pathogenesis of myocardial fibrosis and remodeling during the development of DCM, indicating a potential therapeutic target for DCM treatment.

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