Abstract
BackgroundDilated 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.Methods and ResultsMicroarray 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. ConclusionThis 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.
Highlights
Dilated cardiomyopathy (DCM) is one of the most frequent diseases that cause heart failure (HF) [1]
Among these differentially expressed genes, 13 belonged to the cardiac voltage-gated ion channel activity functional category according to the DAVID programme (Table S2). These genes are responsible for ion trafficking involved in cardiac contraction, an important process compromised in DCM. As this functional category has yet to be characterized in DCM, we focused on 7 of these ion channels (SCN2B, KCNJ5, KCNJ8, CLIC2, CLCN3, CACNB2, and CACNA1C) in this study, based on the described relationship of these channels with the contraction process (Table 2)
It was shown that SCN2B was upregulated, while KCNJ5, KCNJ8, CLIC2, and CACNB2 were downregulated in DCM compared to control donors (CNT) (Figure 2), confirming the microarray results with regard to fold change and significance
Summary
Dilated cardiomyopathy (DCM) is one of the most frequent diseases that cause heart failure (HF) [1]. There are not studies analyzing the mechanisms involved in cardiac contraction dysfunction at the ion channel gene expression level. Cardiac muscle contraction produced by the initiation of action potentials (AP) in cardiomyocytes has an important role in the pathogenesis of the disease. The sarcomere is the functional unit in the contraction process that spans the area between the Z lines. It is made of three types of filaments: thin (actin), thick (myosin), and elastic (titin or connectin) [5]. The aim of the study was to evaluate for the first time the differential gene expression of cardiac ion channels in DCM patients compared to control subjects
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