Myeloid Cells Implicated in Right Ventricular Dysfunction in HFpEF

A study in Circulation investigated whether leukocytes contribute to right ventricular dysfunction in heart failure with preserved ejection fraction (HFpEF). Researchers assigned young and aged male and female mice to chow, HFpEF induction with L-NAME plus a high-fat diet, chronic hypoxia at 10% oxygen, or combined HFpEF induction and hypoxia. They assessed biventricular function and myeloid-cell dynamics, tested myeloid-cell depletion using a colony-stimulating factor 1 receptor inhibitor, and analyzed human HFpEF cohorts, including right ventricular biopsies.

Mice receiving combined HFpEF induction and hypoxia developed left ventricular diastolic dysfunction, right ventricular hypertrophy, elevated right ventricular systolic pressure, and reduced tricuspid annular plane systolic excursion. Right ventricular tissue showed increased leukocyte, monocyte, and macrophage counts. Proteomic analyses supported innate immune activation, while fate mapping identified recruited monocyte-derived macrophages as the predominant cardiac macrophage source in the right ventricle. Myeloid-cell depletion was associated with lower right ventricular systolic pressure than in controls.

Human biopsies showed increased expression of adhesion molecules, fibrotic markers, and inflammatory transcripts, alongside an association between right ventricular dysfunction and CD68-positive cells. These findings support a mechanistic role for myeloid cells in the mouse model, with corresponding inflammatory associations in humans. They do not establish therapeutic efficacy in patients. The available abstract reports no sample sizes or numerical effect estimates, and full text was unavailable for assessment.