BACKGROUND: The role of cardiac mast cells (MCs) in the progression to heart failure has recently become increasingly evident. Cathepsin g is a neutrophil- and mast cell-derived protease, which can convert angiotensin I to angiotensin II and thereby activate the TGF-beta pathway, resulting in myocyte necrosis, hypertrophy, and increased fibrosis. This study focuses on mast cell-derived cathepsin g in the human heart during heart failure and following mechanical unloading by means of heart-assist devices (LVADs). MATERIALS AND METHODS: Myocardial tissue was obtained from 10 patients with end-stage cardiomyopathy at the time of LVAD implantation (pre-LVAD) and following orthotopic heart transplantation (post-LAVD). In addition, biopsies of four normal hearts served as a control group. Paraffin-embedded sections were dual stained for cathepsin g and tryptase, a known marker for mast cells, using standard immunohistochemistry protocols. Total cathepsin g positive mast cells were counted. RESULTS: No cathepsin g positive MCs were found in normal hearts. However, we found evidence for cathepsin g in cardiac MCs in heart failure tissues (pre-LVAD). During heart failure, 46% of total MCs were cathepsin g positive as compared to after mechanical unloading, where only 11% of total MCs were cathepsin g positive (P<0.001). CONCLUSION: Heart failure causes an increase of myocardial MCs. We have provided evidence that cathepsin g positive MCs accumulate during heart failure and their total percentage decreases after ventricular unloading. This coincides with the decrease in myocyte necrosis, hypertrophy, and fibrosis. Thus, cathepsin g may play a role in the progression to heart failure by activating angiotensin II, leading to detrimental effects on the heart.
BACKGROUND: The role of cardiac mast cells (MCs) in the progression to heart failure has recently become increasingly evident. Cathepsin g is a neutrophil- and mast cell-derived protease, which can convert angiotensin I to angiotensin II and thereby activate the TGF-beta pathway, resulting in myocyte necrosis, hypertrophy, and increased fibrosis. This study focuses on mast cell-derived cathepsin g in the human heart during heart failure and following mechanical unloading by means of heart-assist devices (LVADs). MATERIALS AND METHODS: Myocardial tissue was obtained from 10 patients with end-stage cardiomyopathy at the time of LVAD implantation (pre-LVAD) and following orthotopic heart transplantation (post-LAVD). In addition, biopsies of four normal hearts served as a control group. Paraffin-embedded sections were dual stained for cathepsin g and tryptase, a known marker for mast cells, using standard immunohistochemistry protocols. Total cathepsin g positive mast cells were counted. RESULTS: No cathepsin g positive MCs were found in normal hearts. However, we found evidence for cathepsin g in cardiac MCs in heart failure tissues (pre-LVAD). During heart failure, 46% of total MCs were cathepsin g positive as compared to after mechanical unloading, where only 11% of total MCs were cathepsin g positive (P<0.001). CONCLUSION:Heart failure causes an increase of myocardial MCs. We have provided evidence that cathepsin g positive MCs accumulate during heart failure and their total percentage decreases after ventricular unloading. This coincides with the decrease in myocyte necrosis, hypertrophy, and fibrosis. Thus, cathepsin g may play a role in the progression to heart failure by activating angiotensin II, leading to detrimental effects on the heart.
Authors: Carlos M Ferrario; Sarfaraz Ahmad; Jasmina Varagic; Che Ping Cheng; Leanne Groban; Hao Wang; James F Collawn; Louis J Dell Italia Journal: Am J Physiol Heart Circ Physiol Date: 2016-05-27 Impact factor: 4.733
Authors: S I Lok; D J Lok; P van der Weide; B Winkens; P W Bruggink-André de la Porte; P A Doevendans; R A de Weger; P van der Meer; N de Jonge Journal: Neth Heart J Date: 2014-09 Impact factor: 2.380