Fedak, PaulNgu, Janet2013-04-302014-05-012013-04-302013http://hdl.handle.net/11023/659After a myocardial infarction, extracellular matrix (ECM) dysregulation leads to maladaptive cardiac remodeling that constitutes the basis of development of heart failure. Tissue Inhibitor of Metalloproteinase-2 (TIMP-2) is an endogenous biomolecule that is critical in the maintenance of ECM architecture. Cardiac fibroblasts are the main cell type that regulates ECM homeostasis. This study employed an innovative method of three-dimensional collagen gel assay, which mimics the natural in vivo ECM. We investigated the effect of TIMP-2 on the human cardiac fibroblast-mediated ECM remodeling. TIMP-2 induced differentiation of cardiac fibroblasts into myofibroblasts that are active in collagen synthesis. Concurrently, TIMP-2 induced an increase in the total protease activity within the collagen gel microenvironment. TIMP-2 did not promote a fibrotic response, despite its ability to activate myofibroblasts. These actions appear to be independent of its MMP-inhibitory actions. In conclusion, TIMP-2 promotes ECM homeostasis via simultaneous induction of myofibroblast activation and total protease activity.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.Medicine and SurgeryHeart FailureExtracellular MatrixTissue Inhibitor of Metalloproteinase-2HumanCardiac Fibroblastsmaster thesis10.11575/PRISM/27687