BACKGROUND: Mast cells are multifunctional cells containing various mediators 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 incubated with mast cell granules (MCGs) for 24 hours. The highest concentration of diluted MCGs caused the death of approximately 70% of cardiomyocytes. This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against 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 proliferation 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 suggest that mast cell chymase may play a role in the progression of heart failure, because loss of cardiomyocytes and proliferation of nonmyocardial cells exaggerate its pathophysiology.
BACKGROUND: Mast cells are multifunctional cells containing various mediators 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 incubated with mast cell granules (MCGs) for 24 hours. The highest concentration of diluted MCGs caused the death of approximately 70% of cardiomyocytes. This cell death was proved to be apoptosis, as quantified by electron microscopy and biochemical criteria. MCG-mediated cytotoxicity was prevented by pretreatment of MCGs with protease inhibitors or a neutralizing antibody against 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 proliferation 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 suggest that mast cell chymase may play a role in the progression of heart failure, because loss of cardiomyocytes and proliferation of nonmyocardial cells exaggerate its pathophysiology.
Authors: Thor Tejada; Lin Tan; Rebecca A Torres; John W Calvert; Jonathan P Lambert; Madiha Zaidi; Murtaza Husain; Maria D Berce; Hussain Naib; Gunnar Pejler; Magnus Abrink; Robert M Graham; David J Lefer; Nawazish Naqvi; Ahsan Husain Journal: Proc Natl Acad Sci U S A Date: 2016-06-06 Impact factor: 11.205
Authors: Bahman Hooshdaran; Mikhail A Kolpakov; Xinji Guo; Sonni A Miller; Tao Wang; Douglas G Tilley; Khadija Rafiq; Abdelkarim Sabri Journal: Basic Res Cardiol Date: 2017-09-14 Impact factor: 17.165
Authors: Maria A Mitry; Dimitri Laurent; Britny L Keith; Elizabeth Sira; Carol A Eisenberg; Leonard M Eisenberg; Sachindra Joshi; Sachin Gupte; John G Edwards Journal: Am J Physiol Cell Physiol Date: 2020-01-08 Impact factor: 4.249
Authors: Indroneal Banerjee; Katrina Carrion; Ricardo Serrano; Jeffrey Dyo; Roman Sasik; Sean Lund; Erik Willems; Seema Aceves; Rudolph Meili; Mark Mercola; Ju Chen; Alexander Zambon; Gary Hardiman; Taylor A Doherty; Stephan Lange; Juan C del Álamo; Vishal Nigam Journal: J Mol Cell Cardiol Date: 2014-11-13 Impact factor: 5.000