Mast Cell-Derived Cathepsin g: A Possible Role in The Adverse Remodeling of The Failing Human Heart

Jama Jahanyar, Keith A. Youker, Matthias Loebe, Christian Assad-Kottner, Michael M. Koerner, Guillermo Torre-Amione, George P. Noon

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)199-203
Number of pages5
JournalJournal of Surgical Research
Volume140
Issue number2
DOIs
StatePublished - May 15 2007
Externally publishedYes

Keywords

  • LVAD
  • cathepsin g
  • chymase
  • heart failure
  • mast cells
  • remodeling

ASJC Scopus subject areas

  • Surgery

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    Jahanyar, J., Youker, K. A., Loebe, M., Assad-Kottner, C., Koerner, M. M., Torre-Amione, G., & Noon, G. P. (2007). Mast Cell-Derived Cathepsin g: A Possible Role in The Adverse Remodeling of The Failing Human Heart. Journal of Surgical Research, 140(2), 199-203. https://doi.org/10.1016/j.jss.2007.02.040