Altered mitochondrial expression genes in patients receiving right ventricular apical pacing

Abstract

Left ventricular mechanical dyssynchrony from right ventricular apical (RVA) pacing may lead to heart failure. Mitochondrial dysfunction has been observed in the failing heart; however, whether RVA pacing may alter the underlying mitochondrial dynamics at an early stage in patients with preserved ejection fraction is not well understood. RNA was isolated from peripheral whole blood samples of 13 patients. The differentially expressed mRNA profiles from 58 samples (13 experimental subjects; 35 control subjects) were performed using Affymetrix array. Finally, a five-gene signature was identified. DAVID was performed to explore the biological functions of target genes with altered gene expression between two groups. The gene signature (OPA1, CTSA, NDUFA1, STK10 and PRDX1) was able to identify patients post-implant with an area under receiver operating characteristic curve of 0.90 in this study. Our test showed that the gene signature had a sensitivity of 91% with a specificity of 86% in discrimination between post-implant group and healthy controls. In the cellular component category, four genes of the five-gene signature except STK10 were related to mitochondrion. The five-gene signature was associated with oxidative phosphorylation, mitochondrial ATP synthesis and apoptosis in biological process analysis. Pathway analysis indicated that a significant enrichment of candidate genes involved in the calcium signaling and glycosphingolipid biosynthesis pathways. The expression changes observed in this study reflect a profound effect of ventricular mechanical dyssynchrony caused by RVA pacing on the transcriptome at an early stage. RVA pacing alters cellular energy metabolism may have association with mitochondrial dynamics.