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Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function

Alterations in myocardial structure and reduced cardiomyocyte adhesions have been previously described in dilated cardiomyopathy (DCM). We studied the transcriptome of cell adhesion molecules in these patients and their relationships with left ventricular (LV) function decay. We also visualized the...

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Autores principales: Ortega, Ana, Tarazón, Estefanía, Gil-Cayuela, Carolina, García-Manzanares, María, Martínez-Dolz, Luis, Lago, Francisca, González-Juanatey, José Ramón, Cinca, Juan, Jorge, Esther, Portolés, Manuel, Roselló-Lletí, Esther, Rivera, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608295/
https://www.ncbi.nlm.nih.gov/pubmed/28934278
http://dx.doi.org/10.1371/journal.pone.0185062
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author Ortega, Ana
Tarazón, Estefanía
Gil-Cayuela, Carolina
García-Manzanares, María
Martínez-Dolz, Luis
Lago, Francisca
González-Juanatey, José Ramón
Cinca, Juan
Jorge, Esther
Portolés, Manuel
Roselló-Lletí, Esther
Rivera, Miguel
author_facet Ortega, Ana
Tarazón, Estefanía
Gil-Cayuela, Carolina
García-Manzanares, María
Martínez-Dolz, Luis
Lago, Francisca
González-Juanatey, José Ramón
Cinca, Juan
Jorge, Esther
Portolés, Manuel
Roselló-Lletí, Esther
Rivera, Miguel
author_sort Ortega, Ana
collection PubMed
description Alterations in myocardial structure and reduced cardiomyocyte adhesions have been previously described in dilated cardiomyopathy (DCM). We studied the transcriptome of cell adhesion molecules in these patients and their relationships with left ventricular (LV) function decay. We also visualized the intercalated disc (ID) structure and organization. The transcriptomic profile of 23 explanted LV samples was analyzed using RNA-sequencing (13 DCM, 10 control [CNT]), focusing on cell adhesion genes. Electron microscopy analysis to visualize ID structural differences and immunohistochemistry experiments of ID proteins was also performed. RT-qPCR and western blot experiments were carried out on ID components. We found 29 differentially expressed genes, most of all, constituents of the ID structure. We found that the expression of GJA3, DSP and CTNNA3 was directly associated with LV ejection fraction (r = 0.741, P = 0.004; r = 0.674, P = 0.011 and r = 0.565, P = 0.044, respectively), LV systolic (P = 0.003, P = 0.003, P = 0.028, respectively) and diastolic dimensions (P = 0.006, P = 0.001, P = 0.025, respectively). Electron microscopy micrographs showed a reduced ID convolution index and immunogold labeling of connexin 46 (GJA gene), desmoplakin (DSP gene) and catenin α-3 (CTNNA3 gene) proteins in DCM patients. Moreover, we observed that protein and mRNA levels analyzed by RT-qPCR of these ID components were diminished in DCM group. In conclusion, we report significant gene and protein expression changes and found that the ID components GJA3, DSP and CTNNA3 were highly related to LV function. Microscopic observations indicated that ID is structurally compromised in these patients. These findings give new data for understanding the ventricular depression that characterizes DCM, opening new therapeutic perspectives for these critically diseased patients.
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spelling pubmed-56082952017-10-09 Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function Ortega, Ana Tarazón, Estefanía Gil-Cayuela, Carolina García-Manzanares, María Martínez-Dolz, Luis Lago, Francisca González-Juanatey, José Ramón Cinca, Juan Jorge, Esther Portolés, Manuel Roselló-Lletí, Esther Rivera, Miguel PLoS One Research Article Alterations in myocardial structure and reduced cardiomyocyte adhesions have been previously described in dilated cardiomyopathy (DCM). We studied the transcriptome of cell adhesion molecules in these patients and their relationships with left ventricular (LV) function decay. We also visualized the intercalated disc (ID) structure and organization. The transcriptomic profile of 23 explanted LV samples was analyzed using RNA-sequencing (13 DCM, 10 control [CNT]), focusing on cell adhesion genes. Electron microscopy analysis to visualize ID structural differences and immunohistochemistry experiments of ID proteins was also performed. RT-qPCR and western blot experiments were carried out on ID components. We found 29 differentially expressed genes, most of all, constituents of the ID structure. We found that the expression of GJA3, DSP and CTNNA3 was directly associated with LV ejection fraction (r = 0.741, P = 0.004; r = 0.674, P = 0.011 and r = 0.565, P = 0.044, respectively), LV systolic (P = 0.003, P = 0.003, P = 0.028, respectively) and diastolic dimensions (P = 0.006, P = 0.001, P = 0.025, respectively). Electron microscopy micrographs showed a reduced ID convolution index and immunogold labeling of connexin 46 (GJA gene), desmoplakin (DSP gene) and catenin α-3 (CTNNA3 gene) proteins in DCM patients. Moreover, we observed that protein and mRNA levels analyzed by RT-qPCR of these ID components were diminished in DCM group. In conclusion, we report significant gene and protein expression changes and found that the ID components GJA3, DSP and CTNNA3 were highly related to LV function. Microscopic observations indicated that ID is structurally compromised in these patients. These findings give new data for understanding the ventricular depression that characterizes DCM, opening new therapeutic perspectives for these critically diseased patients. Public Library of Science 2017-09-21 /pmc/articles/PMC5608295/ /pubmed/28934278 http://dx.doi.org/10.1371/journal.pone.0185062 Text en © 2017 Ortega et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ortega, Ana
Tarazón, Estefanía
Gil-Cayuela, Carolina
García-Manzanares, María
Martínez-Dolz, Luis
Lago, Francisca
González-Juanatey, José Ramón
Cinca, Juan
Jorge, Esther
Portolés, Manuel
Roselló-Lletí, Esther
Rivera, Miguel
Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function
title Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function
title_full Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function
title_fullStr Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function
title_full_unstemmed Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function
title_short Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function
title_sort intercalated disc in failing hearts from patients with dilated cardiomyopathy: its role in the depressed left ventricular function
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608295/
https://www.ncbi.nlm.nih.gov/pubmed/28934278
http://dx.doi.org/10.1371/journal.pone.0185062
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