Mast cells participate in the development of diastolic dysfunction in diabetic obese mice

Rational Heart failure with preserved ejection fraction (HFpEF) is a growing epidemiologic issue. However, to date, its pathophysiology remains poorly understood.Objective Our goal was to investigate the role of microvessel disease in the pathophysiology of diastolic dysfunction.Findings To do so, we used Leptin receptor deficient (Leprdb/db) female mice as a model of diastolic dysfunction. In these mice, the increased end diastolic pressure (EDP) signing diastolic dysfunction is associated with vascular leakage, endothelial cell activation and leucocyte infiltration. Strikingly, a RNA sequencing analysis of the cardiac vascular fraction of both Leprdb/db and control female mice confirmed endothelial dysfunction and systemic inflammation but also revealed a strong increase in several mast cell markers (notably FceR1a, Tryptase and Chymase). We then histologically confirmed an accumulation of activated mast cells in the heart of Leprdb/db mice. Importantly, mast cell degranulation inhibition reduced EDP, vascular leakage and leucocyte infiltration in Leprdb/db mice.Conclusion Mast cells play a critical role in the development of cardiac microvessel disease and diastolic dysfunction.Competing Interest StatementThe authors have declared no competing interest.View Full Text