Circulating Immune Cell Signature Analysis in HFpEF Across Species.

Area of Science:

• Immunology
• Cardiology
• Genomics

Background:

• Heart failure with preserved ejection fraction (HFpEF) is linked to systemic inflammation and comorbidities like obesity and hypertension.
• Previous research indicated intramyocardial inflammation in HFpEF, suggesting systemic inflammatory processes with specific patterns.

Purpose of the Study:

• To investigate the immune cell transcriptional landscape in HFpEF patients and compare it to heart failure with reduced ejection fraction (HFrEF) and healthy controls.
• To validate findings in a preclinical HFpEF mouse model and assess the therapeutic potential of an anti-inflammatory agent.

Main Methods:

• Single-cell RNA sequencing of peripheral blood mononuclear cells from HFpEF patients, HFrEF patients, and healthy controls.
• Bulk RNA sequencing of whole blood samples for validation.
• Investigated an HFpEF mouse model induced by high-fat diet and L-NAME, with and without nitro-oleic acid (NO2-OA) treatment.

Main Results:

• HFpEF patients exhibited a distinct inflammatory immune cell signature in peripheral blood, with obesity-related cytokine gene expression and obesity-independent mitochondrial activity.
• The HFpEF mouse model displayed similar inflammatory marker increases.
• Nitro-oleic acid treatment partially normalized immune signatures and improved diastolic function in the mouse model.

Conclusions:

• HFpEF is characterized by a unique immune cell transcriptional signature, distinct from HFrEF.
• Conserved immune signatures across human and murine models suggest shared mechanisms.
• The positive effect of nitro-oleic acid in the preclinical model offers translational insights for personalized HFpEF interventions.