Left Ventricular Gene Expression in Heart Failure With Preserved Ejection Fraction-Profibrotic and Proinflammatory...

Area of Science:

• Cardiology
• Molecular Biology
• Genomics

Background:

• Heart failure with preserved ejection fraction (HFpEF) is a growing clinical challenge with limited therapeutic options.
• The precise molecular mechanisms driving HFpEF pathogenesis remain poorly understood.
• Proinflammatory pathways have been hypothesized to contribute to cardiac fibrosis in HFpEF.

Purpose of the Study:

• To investigate the molecular underpinnings of HFpEF by comparing gene expression profiles in patient and control myocardial tissue.
• To assess the role of proinflammatory and profibrotic signaling pathways in the development of HFpEF.

Main Methods:

• Epicardial left ventricular biopsies were obtained from HFpEF patients and matched controls during coronary artery bypass surgery.
• RNA sequencing was performed on flash-frozen myocardial tissue to generate comprehensive left ventricular transcriptomes.
• Unsupervised analysis compared gene expression patterns between HFpEF and control groups.

Main Results:

• HFpEF patients exhibited distinct demographic and clinical characteristics, including hypertension, higher BMI, and elevated NT-proBNP levels compared to controls.
• Transcriptome analysis identified 477 differentially expressed genes in HFpEF.
• These genes were predominantly associated with profibrotic pathways, specifically extracellular matrix production and posttranslational modification, with no evidence of a proinflammatory signature.

Conclusions:

• The gene expression profile in HFpEF left ventricular myocardium confirms significant extracellular matrix gene upregulation, indicative of myocardial fibrosis.
• Contrary to hypotheses, activated proinflammatory pathways were not identified as a key feature in the studied HFpEF cohort.
• These findings highlight profibrotic mechanisms as central to HFpEF pathophysiology, distinct from inflammatory processes.