Neutrophil arrest in myocardial capillaries drives hypoxia and impairs diastolic function in a mouse model of heart failure with preserved ejection fraction
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Myocardial blood flow deficits in heart failure with preserved ejection fraction (HFpEF) patients and related animal models have been recognized for decades, but the underlying mechanisms and resulting consequences for HFpEF pathogenesis remain poorly understood. Using intravital cardiac microcopy in a ‘two-hit’ mouse model of HFpEF, we identified an increased number of neutrophils in capillaries slow moving orstalled, blocking blood flow, as compared to control mice. Administration of antibodies against the neutrophil marker Ly6G reduced the number of arrested neutrophils in myocardial capillaries, leading to both a reduction in myocardial tissue hypoxia and improvement in diastolic function and exercise tolerance. This study identifies a previously uncharacterized cellular mechanism that explains myocardial blood flow deficits in mouse models of HFpEF, and demonstrates that improving myocardial blood flow improves heart function. Restoring myocardial perfusion by preventing neutrophil arrest in coronary capillaries may provide a strategy for improving heart function in HFpEF patients.
