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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2017-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5608295?pdf=render |
| _version_ | 1818486534729367552 |
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| author | Ana Ortega Estefanía Tarazón Carolina Gil-Cayuela María García-Manzanares Luis Martínez-Dolz Francisca Lago José Ramón González-Juanatey Juan Cinca Esther Jorge Manuel Portolés Esther Roselló-Lletí Miguel Rivera |
| author_facet | Ana Ortega Estefanía Tarazón Carolina Gil-Cayuela María García-Manzanares Luis Martínez-Dolz Francisca Lago José Ramón González-Juanatey Juan Cinca Esther Jorge Manuel Portolés Esther Roselló-Lletí Miguel Rivera |
| author_sort | Ana Ortega |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-10T16:24:16Z |
| format | Article |
| id | doaj.art-da28db7bda9b44caaa050bf6f2b2dedb |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T16:24:16Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-da28db7bda9b44caaa050bf6f2b2dedb2022-12-22T01:41:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018506210.1371/journal.pone.0185062Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function.Ana OrtegaEstefanía TarazónCarolina Gil-CayuelaMaría García-ManzanaresLuis Martínez-DolzFrancisca LagoJosé Ramón González-JuanateyJuan CincaEsther JorgeManuel PortolésEsther Roselló-LletíMiguel RiveraAlterations 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.http://europepmc.org/articles/PMC5608295?pdf=render |
| spellingShingle | Ana Ortega Estefanía Tarazón Carolina Gil-Cayuela María García-Manzanares Luis Martínez-Dolz Francisca Lago José Ramón González-Juanatey Juan Cinca Esther Jorge Manuel Portolés Esther Roselló-Lletí Miguel Rivera Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function. PLoS ONE |
| 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 |
| url | http://europepmc.org/articles/PMC5608295?pdf=render |
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