Differential gene expression of cardiac ion channels in human dilated cardiomyopathy

• Published in: PloS one Vol. 8; no. 12; p. e79792
• Main Authors: Molina-Navarro, Maria Micaela, Roselló-Lletí, Esther, Ortega, Ana, Tarazón, Estefanía, Otero, Manuel, Martínez-Dolz, Luis, Lago, Francisca, González-Juanatey, José Ramón, España, Francisco, García-Pavía, Pablo, Montero, José Anastasio, Portolés, Manuel, Rivera, Miguel
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05-12-2013; Public Library of Science (PLoS)
• Subjects: Analysis; Biomedical research; Cardiology; Cardiomyocytes; Cardiomyopathy; Cardiomyopathy, Dilated - genetics; Cardiomyopathy, Dilated - metabolism; Case-Control Studies; Contraction; Dilated cardiomyopathy; Disease; DNA microarrays; Female; Gene expression; Genes; Genomes; Genomics; Heart diseases; Heart failure; Heart surgery; Heart transplantation; Heart transplants; Hospitals; Humans; Ion channels; Ion Channels - genetics; Ion Channels - metabolism; Kinases; Male; Medical research; Middle Aged; Muscle contraction; Myocardial diseases; Myocardium - metabolism; Patients; Proteins; Ribonucleic acid; RNA; Rodents; Transcriptome; Transplantation; Ventricle; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0079792

Dilated cardiomyopathy (DCM) is characterized by idiopathic dilation and systolic contractile dysfunction of the cardiac chambers. The present work aimed to study the alterations in gene expression of ion channels involved in cardiomyocyte function.
Microarray profiling using the Affymetrix Human Gene® 1.0 ST array was performed using 17 RNA samples, 12 from DCM patients undergoing cardiac transplantation and 5 control donors (CNT). The analysis focused on 7 cardiac ion channel genes, since this category has not been previously studied in human DCM. SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C were downregulated. The RT-qPCR (21 DCM and 8 CNT samples) validated the gene expression of SCN2B (p < 0.0001), KCNJ5 (p < 0.05), KCNJ8 (p < 0.05), CLIC2 (p < 0.05), and CACNB2 (p < 0.05). Furthermore, we performed an IPA analysis and we found a functional relationship between the different ion channels studied in this work.
This study shows a differential expression of ion channel genes involved in cardiac contraction in DCM that might partly underlie the changes in left ventricular function observed in these patients. These results could be the basis for new genetic therapeutic approaches.