Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells in vitro

Background-Mast cells are multifunctional cells containing various mediator s such as cytokines, proteases, and histamine. They are found in the human heart and have been implicated in ventricular hypertrophy and heart failure . However, their roles in pathogenesis of these diseases are unknown. Methods and Results-Cultured cardiomyocytes from neonatal rats were incubat ed with mast cell granules (MCGs) for 24 hours, The highest concentration o f diluted MCGs caused the death of approximate to 70% of cardiomyocytes, Th is cell death was proved to be apoptosis, as quantified by electron microsc opy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pr etreatment of MCGs with protease inhibitors or a neutralizing antibody agai nst rat mast cell chymase 1 (RMCP 1), RMCP 1 by itself was proved to induce cell death of cardiomyocytes. These results suggest that RMCP 1 contained in MCGs causes the death of cardiomyocytes, In contrast, MCGs induced the p roliferation of intramyocardial cells other than myocytes. RMCP 1 was also proved to induce their proliferation. Conclusions-Mast cells cause apoptosis of cardiomyocytes and proliferation of other intramyocardial cells via the activity of RMCP 1, Our results sugg est that mast cell chymase may play a role in the progression of heart fail ure, because loss of cardiomyocytes and proliferation of nonmyocardial cell s exaggerate its pathophysiology.