TY - JOUR
T1 - Mast Cell-Derived Cathepsin g
T2 - A Possible Role in The Adverse Remodeling of The Failing Human Heart
AU - Jahanyar, Jama
AU - Youker, Keith A.
AU - Loebe, Matthias
AU - Assad-Kottner, Christian
AU - Koerner, Michael M.
AU - Torre, Guillermo
AU - Noon, George P.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/5/15
Y1 - 2007/5/15
N2 - 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-β 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.
AB - 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-β 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.
KW - cathepsin g
KW - chymase
KW - heart failure
KW - LVAD
KW - mast cells
KW - remodeling
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U2 - 10.1016/j.jss.2007.02.040
DO - 10.1016/j.jss.2007.02.040
M3 - Article
C2 - 17418861
AN - SCOPUS:34248199335
SN - 0022-4804
VL - 140
SP - 199
EP - 203
JO - Journal of Surgical Research
JF - Journal of Surgical Research
IS - 2
ER -