Altered mitochondrial expression genes in patients receiving right ventricular apical pacing

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Right ventricular apical (RVA) pacing can induce left ventricular mechanical dyssynchrony, potentially leading to heart failure.
• Mitochondrial dysfunction is linked to heart failure, but its early changes due to RVA pacing are unclear, especially in patients with preserved ejection fraction.

Purpose of the Study:

• To investigate early alterations in mitochondrial dynamics and gene expression profiles in patients undergoing RVA pacing.
• To identify a gene signature capable of distinguishing RVA pacing patients from healthy controls.

Main Methods:

• RNA was extracted from peripheral whole blood samples of 13 patients and 35 controls.
• Differential mRNA expression profiling was performed using Affymetrix arrays.
• Gene signature identification and pathway analysis were conducted using DAVID tools.

Main Results:

• A five-gene signature (OPA1, CTSA, NDUFA1, STK10, PRDX1) was identified, showing an area under the receiver operating characteristic curve of 0.90.
• The gene signature demonstrated 91% sensitivity and 86% specificity in discriminating between post-RVA pacing patients and controls.
• Four of the five genes are mitochondrion-related, and the signature is associated with oxidative phosphorylation, ATP synthesis, and apoptosis.

Conclusions:

• Ventricular mechanical dyssynchrony from RVA pacing significantly impacts the transcriptome early on.
• The identified gene signature reflects early cellular energy metabolism alterations and potential mitochondrial dynamics changes.
• RVA pacing-induced dyssynchrony may be detectable through peripheral blood gene expression analysis.