PT  - JOURNAL ARTICLE
AU  - Sarah Guimbal
AU  - Lauriane Cornuault
AU  - Pierre-Louis Hollier
AU  - Candice Chapouly
AU  - Marie-Lise Bats
AU  - Alain-Pierre Gadeau
AU  - Thierry Couffinhal
AU  - Marie-Ange Renault
TI  - Mast cells participate in the development of diastolic dysfunction in diabetic obese mice
AID  - 10.1101/2020.06.16.154872
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.16.154872
4099  - http://biorxiv.org/content/early/2020/06/17/2020.06.16.154872.short
4100  - http://biorxiv.org/content/early/2020/06/17/2020.06.16.154872.full
AB  - 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.