Key result
Cromolyn sodium reduces EDP, vascular leakage, and leucocyte infiltration in diabetic obese mice.
Why the study?
Heart failure with preserved ejection fraction is a growing epidemiologic issue, but its pathophysiology remains poorly understood, motivating investigation into the role of microvessel disease in diastolic dysfunction.
Does mast cell degranulation inhibition reduce end diastolic pressure and vascular leakage in a diabetic obese mouse model of diastolic dysfunction?
Does mast cell degranulation inhibition reduce end diastolic pressure and vascular leakage in a diabetic obese mouse model of diastolic dysfunction?
Mast cell degranulation inhibition reduces end diastolic pressure and vascular leakage in a diabetic obese mouse model, suggesting a potential novel therapeutic target for HFpEF.
Hypothesis-generating for mast cell inhibition in HFpEF; leaves open translation from diabetic mouse models to patients.
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 (Lepr db/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 Lepr db/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 Lepr db/db mice. Importantly, mast cell degranulation inhibition reduced EDP, vascular leakage and leucocyte infiltration in Lepr db/db mice. Conclusion Mast cells play a critical role in the development of cardiac microvessel disease and diastolic dysfunction.
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Guimbal et al. (2020) studied Diastolic dysfunction (Heart failure with preserved ejection fraction). Cromolyn sodium vs. 0.9% NaCl (vehicle) was evaluated on End diastolic pressure (EDP). Mast cell degranulation inhibition with cromolyn sodium significantly reduced end diastolic pressure, vascular leakage, and leucocyte infiltration in diabetic obese mice.
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