AIMS: 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. METHODS AND 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. CONCLUSION: Our data indicate that CTSL regulates cardiac repair and remodelling post-MI through a mechanism with multiple pathways.
AIMS: 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. METHODS AND 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. CONCLUSION: Our data indicate that CTSL regulates cardiac repair and remodelling post-MI through a mechanism with multiple pathways.
Authors: Juliane C Campos; Bruno B Queliconi; Luiz H M Bozi; Luiz R G Bechara; Paulo M M Dourado; Allen M Andres; Paulo R Jannig; Kátia M S Gomes; Vanessa O Zambelli; Cibele Rocha-Resende; Silvia Guatimosim; Patricia C Brum; Daria Mochly-Rosen; Roberta A Gottlieb; Alicia J Kowaltowski; Julio C B Ferreira Journal: Autophagy Date: 2017-08-03 Impact factor: 16.016
Authors: Hendrik W van Deventer; Daniela A Palmieri; Qing Ping Wu; Everett C McCook; Jonathan S Serody Journal: J Immunol Date: 2013-03-27 Impact factor: 5.422
Authors: Han Chen; Jing Wang; Mei-Xiang Xiang; Yan Lin; Aina He; Chun-Na Jin; Jian Guan; Galina K Sukhova; Peter Libby; Jian-An Wang; Guo-Ping Shi Journal: Cardiovasc Res Date: 2013-06-14 Impact factor: 10.787