Role of Tissue Inhibitor of Metalloproteinase-2 in Human Cardiac Fibroblast-Mediated Extracellular Matrix Remodeling

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dc.contributor.advisorFedak, Paul
dc.contributor.authorNgu, Janet
dc.date.accessioned2013-04-30T22:15:53Z
dc.date.available2014-05-01T07:00:16Z
dc.date.issued2013-04-30
dc.date.submitted2013en
dc.description.abstractAfter 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.en_US
dc.description.embargoterms12 monthsen_US
dc.identifier.citationNgu, J. (2013). Role of Tissue Inhibitor of Metalloproteinase-2 in Human Cardiac Fibroblast-Mediated Extracellular Matrix Remodeling (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca. doi:10.11575/PRISM/27687en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/27687
dc.identifier.urihttp://hdl.handle.net/11023/659
dc.language.isoeng
dc.publisher.facultyGraduate Studies
dc.publisher.institutionUniversity of Calgaryen
dc.publisher.placeCalgaryen
dc.rightsUniversity 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.
dc.subjectMedicine and Surgery
dc.subject.classificationHeart Failureen_US
dc.subject.classificationExtracellular Matrixen_US
dc.subject.classificationTissue Inhibitor of Metalloproteinase-2en_US
dc.subject.classificationHumanen_US
dc.subject.classificationCardiac Fibroblastsen_US
dc.titleRole of Tissue Inhibitor of Metalloproteinase-2 in Human Cardiac Fibroblast-Mediated Extracellular Matrix Remodeling
dc.typemaster thesis
thesis.degree.disciplineCardiovascular & Respiratory Sciences
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameMaster of Science (MSc)
ucalgary.item.requestcopytrue
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