Primary Screening Of Genes Expression Profiling Of Peripheral Blood Of Patients Receiving Right Ventricular Apical Pacing

BacgroudLeft 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.ObjectivesTo detect altered gene expression of peripheral blood and screen a gene signature after RVA pacing.We expect to explore the biological functions of target genes.MethodsRNA was isolated from peripheral whole blood samples of 13 patients.The differentially expressed mRNA profiles from 23 samples(10 patients pre-implant and post-implant;3patintes pre-implant)were performed using Affymetrix array.Gene expression profiles of RNA samples were imported into Affymetrix the GeneChip Operating System 1.4.1(GCOS)software.Our methodology for data mining was based on our Sentinel Pair algorithm.The area under the receiver operating characteristic curve(ROC AUC)was calculated to assess the ability of each probe set to distinguish the post-implant patients from the pre-implant of pacemaker patients.ResultsThe altered expression genes were loacted in cell membrane and cell connnection.Most of the genes were associated with cell mobility in ion transmembrane transport.Pathway analysis indicated that a significant enrichment of candidate genes involved in the calciumsignaling,including CaMKII2A,RYR2 and IP3R.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.ConclusionsThe expression changes observed in this study reflect a profound effect of ventricular mechanical dyssynchrony caused by RVA pacing on the transcriptome at anearly stage.