Macrophage NLRP3-dependent IL-1β production contributes to aortic fibrosis in heart failure with preserved ejection fraction

• A novel HFpEF mouse model (high-fat diet + aldosterone infusion) recapitulates aortic fibrosis and LV diastolic dysfunction with preserved ejection fraction. • Macrophage recruitment and NLRP3-dependent IL-1β production are augmented in fibrotic aortas of HFpEF mice. • Macrophage-specific NLRP3 deficiency suppresses cleaved-caspase-1 and mature IL-1β, and improves aortic fibrosis and LV diastolic dysfunction. • Targeting macrophage NLRP3 inflammasome may offer a therapeutic strategy for HFpEF-associated aortic stiffness.