Differential Gene Expression Among Patients With Heart Failure Experiencing Pain

Area of Science:

• Genomics
• Cardiology
• Pain Medicine

Background:

• Chronic pain is prevalent in heart failure (HF) patients, worsening outcomes and quality of life.
• The genetic basis of chronic pain in HF remains poorly understood, hindering the development of targeted interventions.

Purpose of the Study:

• To identify genes associated with chronic pain in individuals with heart failure (HF) using messenger RNA (mRNA) sequencing data.
• To explore the mechanistic underpinnings of pain in HF by analyzing gene expression patterns.

Main Methods:

• Analyzed mRNA sequencing data from 40 HF patients with and without pain.
• Utilized DESeq2 for differential gene expression analysis and Metascape for protein-protein interaction (PPI) and pathway analysis.
• Validated key gene candidates in a separate cohort of 24 HF patients using quantitative polymerase chain reaction (qPCR).

Main Results:

• Identified 334 differentially expressed genes between HF patients with and without pain, primarily linked to neutrophil degranulation pathways.
• Pinpointed seven candidate genes from a core PPI network, with MMP8, PCSK9, and DEFA3 showing consistent upregulation in painful HF.
• These seven genes are implicated in immune, inflammatory, and atherosclerotic processes.

Conclusions:

• The study identifies MMP8, PCSK9, and DEFA3 as potential key genes contributing to chronic pain mechanisms in heart failure.
• These findings provide a foundation for further research into novel therapeutic strategies for pain management in HF.
• Further investigation is warranted to validate these genes across distinct pain phenotypes in HF.