Mast Cells, the Allergic Responders, a Target of Heart Failure Therapy?

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Introduction: Increased cardiac demand leads to an adaptive and compensatory remodeling. The presence of continual stress such as pressure overload, volume overload, cardiac injury and metabolic stress leads to a maladaptive cardiac remodeling and heart failure (HF). The different causes of cardiac maladaptive remodeling likely share common molecular, biochemical, and mechanical pathways. Cardiomyocytes, fibroblasts, inflammatory cells, coronary vasculature and extra cellular matrix participate in the remodeling events. Here we focus on mast cells in the remodeling process using a model of HF after cardiac injury, i.e., autoimmune myocarditis. Methods: Rats were immunized with pig cardiac myosin to develop experimental autoimmune myocarditis, which eventually resulted in HF. Twenty eight days after cardiac myosin immunization, one group of rats was treated with disodium cromoglycate (DSCG), a mast cell stabilizer, at 24mg/Kg until sacrifice (n=17). Another group of animals was treated with vehicle for the same period (n=13). Evaluations of cardiac hypertrophy, myocardial fibrosis, mast cell density and their degranulation were performed by histopathology, immunostaining and immunoblotting and also cardiac functions by echocardiography and hemodynamic analysis. Results: Increase in mast cell density, cardiac hypertrophy and myocardial fibrosis was observed in the hearts of vehicle-treated postmyocarditis rats. Elevated levels of stem cell factor and tumor necrosis factor-a were found in the hearts of vehicle-treated animals. Decline in myocardial function was observed in the vehicle-treated rats. Importantly, stabilization of mast cells by DSCG reversed all these effects. Conclusions: Our data suggest that cardiac mast cells can be possible therapeutic target in postmyocarditis heart failure.