Gene expression analysis of cation channels involved in cardiac contraction in human dilated cardiomyopathy

Abstract

Purpose: Dilated Cardiomyopathy (DCM) is one of the most frequent causes of Heart Failure (HF). Due to cardiac ion channels are responsible for the contraction and dilation of heart muscle, the aim of this study is to analyze the gene expression of three of the most important ion channels involved in the contraction process, in DCM compared to control group (CNT). Methods: RNA samples were obtained of 42 explanted human hearts (DCM=31; CNT=11) to obtain a microarray profiling. To validate the microarray results a RT-qPCR was performed and Western blot analyses were carried out to evaluate protein levels. Results: We analyzed the gene expression of three of the most important genes involved in the depolarization process of cardiac contraction, encoding calcium (CACNA1C, CACNB2) and sodium (SCN2B) channels. Microarray profiling showed the downregulation of both calcium channels (CACNA1C p<0.01; CACNB2 p<0.001) and the upregulation of the sodium channel SCN2B (p<0.0001). Validation of the results by RT-qPCR showed a high degree of consistency with microarray data. Moreover, we analyzed the proteins encoded by the ion channel genes to study whether the differential gene expression resulted in changes at the protein level. Furthermore, we found an inverse correlation between the mRNA of CACNA1C (p<0.05, r=0.613) and CACNB2 (p<0.05, r=0.615) with basic left ventricular function parameters (left ventricular end diastolic and end systolic dimensions). Conclusions: We show that expression of genes encoding calcium and sodium ion channels is altered in patients with DCM. Additionally, we found and inverse relationship between the expression of calcium genes of patients with DCM, and left ventricular function parameters. All these results could provide a new base for therapeutic approaches since these genes are involved in the contraction of the cardiomyocyte, process impaired in patients with DCM.