Mast Cells Are the Trigger of Small Vessel Disease and Diastolic Dysfunction in Diabetic Obese Mice

Objective: Heart failure with preserved ejection fraction is a major health care issue which has been difficult to manage date, due its complex and not well understood pathophysiology. Specifically, if wealth of literature focuses on heart cardiac component, very little information can be found vascular component. Our goal unravel the critical role small vessel disease in pathophysiology diastolic dysfunction. Approach Results: To do so, we used leptin receptor deficient (Lepr db/db ) female mice, recognized model In these increased end-diastolic pressure signing dysfunction associated leakage, endothelial cell activation, leucocyte infiltration. Strikingly, RNA sequencing analysis both Lepr control mice confirmed systemic inflammation, but above all, revealed strong increase several mast markers (notably FceR1a [high affinity immunoglobulin epsilon subunit ?], tryptase, chymase). We then this accumulation activated cells via histology. Importantly, that degranulation inhibition specific histamine blockade reduced infiltration, subsequently mice. This demonstrated, for first time, cells, release, participate development leading Conclusions: Cardiac key mechanism targeted prevent occurrence dysfunction, by using stabilizers antihistaminic drugs.