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dc.contributor.supervisorDixon, Ian (Physiology and Pathophysiology)en_US
dc.contributor.authorDavies, Jared
dc.date.accessioned2015-09-01T14:54:23Z
dc.date.available2015-09-01T14:54:23Z
dc.date.issued2015
dc.identifier.urihttp://hdl.handle.net/1993/30695
dc.description.abstractOne of the hallmarks of chronic cardiac disease is the excessive formation of fibrous extracellular matrix. This inappropriate remodeling is mediated in large part by cardiac fibroblasts and phenoconverted myofibroblasts. The protooncoprotein Ski has previously been described as possessing anti-fibrotic properties within the myocardium, in addition to triggering apoptosis when overexpressed. In the current study, we found that overexpression of Ski results in a set of distinct morphological and biochemical changes within primary cardiac myofibroblasts that is indicative of apoptosis. Its upregulation is associated with the expression of pro-apoptotic factors such as Bax and Bak, as well as caspase-9 and -7. In all, our results indicate that Ski triggers a pro-death mechanism in primary rat cardiac myofibroblasts that is mediated through the intrinsic apoptotic pathway. The survival of these cells appears to be prolonged by a pro-survival autophagic response as apoptosis is hastened when autophagy is inhibited. The observed cell death response is likely working in parallel with the previously observed anti-fibrotic properties of Ski within this cell type. As myofibroblast cells are the engines of matrix expansion in heart failure, we suggest that using Ski or a projected Ski-mimetic to induce graded apoptosis in myofibroblasts within the failing heart may be a novel therapeutic mechanism of controlling cardiac fibrosis.en_US
dc.language.isoengen_US
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectFibrosisen_US
dc.subjectApoptosisen_US
dc.subjectCardiacen_US
dc.subjectFibroblastsen_US
dc.subjectHearten_US
dc.subjectAuthophagyen_US
dc.titleMechanisms of ski-induced apoptosis in cardiac fibroblasts and myofibroblastsen_US
dc.typeinfo:eu-repo/semantics/masterThesis
dc.typemaster thesisen_US
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.contributor.examiningcommitteeWigle, Jeffrey (Biochemistry and Medical Genetics) Czubryt, Michael (Physiology and Pathophysiology) Halayko, Andrew (Physiology and Pathophysiology)en_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.noteOctober 2015en_US


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