CCR2 + monocyte-derived macrophages drive cardiac hypertrophy in early HFpEF

Development of a multi-comorbidity model induces early heart failure with preserved ejection fraction (HFpEF) in male mice. Early HFpEF is marked by circulating proinflammatory monocytosis (Ly6C hi ) and a disruption in the balance between monocyte-derived macrophage infiltration (CCR2 + ) and resident macrophages (TIMD4 + ). Ablation of CCR2, which prevents recruitment of classical macrophages, improves left ventricle (LV) hypertrophy in early HFpEF but not cardiac fibrosis or diastolic dysfunction. Anti-inflammatory therapies alone, without antifibrotic treatment, will likely not prevent the development of HFpEF.