title: Mast cell-derived cathepsin g: a possible role in the adverse remodeling of the failing human heart.
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-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).
  
  
  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).
  
  
  CONCLUSIONS
  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.affiliation: Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA. jahanyar@bcm.tmc.edu
authors.forename: Jama
authors.initials: J
authors.lastname: Jahanyar
authors.forename: Keith A
authors.initials: KA
authors.lastname: Youker
authors.forename: Matthias
authors.initials: M
authors.lastname: Loebe
authors.forename: Christian
authors.initials: C
authors.lastname: Assad-Kottner
authors.forename: Michael M
authors.initials: MM
authors.lastname: Koerner
authors.forename: Guillermo
authors.initials: G
authors.lastname: Torre-Amione
authors.forename: George P
authors.initials: GP
authors.lastname: Noon
mesh_terms: D000328:Adult; D000368:Aged; D000804:Angiotensin II / Q000378:metabolism; D002303:Cardiac Output, Low / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D016022:Case-Control Studies; D056649:Cathepsin G; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000502:physiology*; D053818:Chymases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis / Q000517:prevention & control; D012697:Serine Endopeptidases / Q000502:physiology*; D053802:Tryptases / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D000804:Angiotensin II; D002403:Cathepsins; D012697:Serine Endopeptidases; C534094:CTSG protein, human; D056649:Cathepsin G; D053818:Chymases; D053802:Tryptases