title: Cathepsin-L contributes to cardiac repair and remodelling post-infarction.
abstract: OBJECTIVE
  Cathepsin-L (CTSL) is a member of the lysozomal cysteine protease family, which participates in remodelling of various tissues. Herein, we sought to examine the potential regulation of CTSL in cardiac remodelling post-infarction.
  
  
  RESULTS
  Experimental myocardial infarction (MI) was created in CTSL-deficient (Ctsl(-/-)) mice (B6 × FSB/GnEi a/a Ctsl(fs)/J) and wild-type littermates (Ctsl(+/+)) by left coronary artery ligation. At days 3, 7, 14, and 28 post-MI, we monitored survival rate and evaluated cardiac function, morphology, and molecular endpoints of repair and remodelling. Survival was 56% in Ctsl(-/-) mice in contrast to 80% (P < 0.05) in Ctsl(+/+) mice post-MI by day 28. The Ctsl(-/-) mice exhibited greater scar dilatation, wall thinning, and worse cardiac dysfunction when compared with Ctsl(+/+) mice. Cardiac matrix metallopeptidase-9 (MMP-9) activity was also diminished, and c-kit-positive cells, natural killer cells, fibrocytes, and monocytes mobilized to peripheral blood and deposited to the infarcted myocardium were significantly decreased in Ctsl(-/-) mice. Furthermore, the local inflammatory response, and granulocyte-colony stimulating factor, stem cell factor (SCF), and stromal cell-derived factor-1 (SDF-1α) expression, as well as cell proliferation, revascularization, and myofibroblast deposition were significantly decreased in Ctsl(-/-) mice compared with Ctsl(+/+) mice.
  
  
  CONCLUSIONS
  Our data indicate that CTSL regulates cardiac repair and remodelling post-MI through a mechanism with multiple pathways.
authors.affiliation: Division of Cardiology, Heart and Stroke/Richard Lewar Centre of Excellence, University Health Network, Toronto General Hospital, 200 Elizabeth Street, Toronto, ON, Canada.
authors.forename: Mei
authors.initials: M
authors.lastname: Sun
authors.forename: Manyin
authors.initials: M
authors.lastname: Chen
authors.forename: Youan
authors.initials: Y
authors.lastname: Liu
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukuoka
authors.forename: Kim
authors.initials: K
authors.lastname: Zhou
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.forename: Fayez
authors.initials: F
authors.lastname: Dawood
authors.forename: Anthony
authors.initials: A
authors.lastname: Gramolini
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000201:enzymology / Q000276:immunology; D056668:Cathepsin L / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004549:Elastin / Q000378:metabolism; D042783:Endothelial Cells / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000201:enzymology* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D058628:Myofibroblasts / Q000201:enzymology / Q000473:pathology; D018919:Neovascularization, Physiologic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D016207:Cytokines; D003094:Collagen; D004549:Elastin; D019009:Proto-Oncogene Proteins c-kit; D056668:Cathepsin L; C534278:Ctsl protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse