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Aims  Disruptions in cardiac ion channels have shown to influence the impaired cardiac contraction in heart failure. We sought to determine the altered gene expression profile of this category in dilated cardiomyopathy (DCM) patients and relate the altered gene expression with the clinical signs present in our patients, such as ventricular dysfunction and sustained monomorphic ventricular tachycardia (SMVT).    Methods and Results  Left ventricular (LV) tissue samples were used in RNA-sequencing technique to elucidate the transcriptomic changes of 13 DCM patients compared to controls (n = 10). We analyzed the differential gene expression of cardiac ion channels, and we found a total of 34 altered genes. We found that the calcium channel CACNG8 mRNA and protein levels were down-regulated and highly and inversely related with LV ejection fraction (LVEF) (r = –0.78,  P <0.01). Furthermore, the potassium channels KCNN3 and KCNJ2 mRNA and protein levels were up-regulated and showed also a significant and inverse correlation with LVEF (r = –0.61,  P <0.05; r = –0.60,  P <0.05) in patients with SMVT.    Conclusion  A broad set of deregulated genes have been identified by RNA-sequencing technique. The relationship of  CACNG8 ,  KCNN3  and  KCNJ2  with LVEF, and the up-regulation of  KCNN3  and  KCNJ2  in all patients with SMVT, irrespective of  CACNG8  expression, suggest a significant role for these three ion flux related genes in the LV dysfunction present in this cardiomyopathy and an important relationship between  KCNN3  and  KCNJ2  up-regulation and the presence of SMVT.

plos one

Patients with Dilated Cardiomyopathy and Sustained Monomorphic Ventricular Tachycardia Show Up-Regulation of KCNN3 and KCNJ2 Genes and CACNG8-Linked Left Ventricular Dysfunction