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Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy
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 progressi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780177/ https://www.ncbi.nlm.nih.gov/pubmed/29115553 http://dx.doi.org/10.3892/mmr.2017.8013 |
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author | Xie, Yeqing Liao, Jianquan Yu, Yong Guo, Qi Yang, Yingzhen Ge, Junbo Chen, Haozhu Chen, Ruizhen |
author_facet | Xie, Yeqing Liao, Jianquan Yu, Yong Guo, Qi Yang, Yingzhen Ge, Junbo Chen, Haozhu Chen, Ruizhen |
author_sort | Xie, Yeqing |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5780177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-57801772018-02-05 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 Mol Med Rep Articles 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. D.A. Spandidos 2018-01 2017-11-08 /pmc/articles/PMC5780177/ /pubmed/29115553 http://dx.doi.org/10.3892/mmr.2017.8013 Text en Copyright: © Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Xie, Yeqing Liao, Jianquan Yu, Yong Guo, Qi Yang, Yingzhen Ge, Junbo Chen, Haozhu Chen, Ruizhen Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
title | Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
title_full | Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
title_fullStr | Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
title_full_unstemmed | Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
title_short | Endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
title_sort | endothelial-to-mesenchymal transition in human idiopathic dilated cardiomyopathy |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5780177/ https://www.ncbi.nlm.nih.gov/pubmed/29115553 http://dx.doi.org/10.3892/mmr.2017.8013 |
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