Intercalated disc in failing hearts from patients with dilated cardiomyopathy : Its role in the depressed left ventricular function
Ortega, Ana (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
Tarazón, Estefanía (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
Gil-Cayuela, Carolina (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
García-Manzanares, María (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
Martínez-Dolz, Luis (Hospital Universitari i Politècnic La Fe (València))
Lago, Francisca (Complejo Hospitalario Universitario de Santiago de Compostela)
González-Juanatey, José Ramón (Complejo Hospitalario Universitario de Santiago de Compostela)
Cinca, Juan (Institut d'Investigació Biomèdica Sant Pau)
Jorge, Esther (Hospital de la Santa Creu i Sant Pau (Barcelona, Catalunya))
Portolés, Manuel (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
Roselló-Lletí, Esther (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
Rivera, Miguel (Centre de Xarxa d'Investigació Biomèdica en Malalties Cardiovasculars (CIBERCV))
Universitat Autònoma de Barcelona

Date:	2017
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI13/00100 Ministerio de Economía y Competitividad PI14/01506 Ministerio de Economía y Competitividad CB16/11/00261
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PloS one, Vol. 12 Núm. 9 (september 2017) , p. e0185062, ISSN 1932-6203

DOI: 10.1371/journal.pone.0185062
PMID: 28934278

16 p, 18.7 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles