The Role of Empagliflozin in Cardiac Fibroblast-Mediated Extracellular Matrix Remodeling

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dc.contributor.advisorFedak, Paul
dc.contributor.authorKang, Sean
dc.contributor.committeememberDuff, Henry J.
dc.contributor.committeememberTibbles, Lee Anne
dc.date2019-06
dc.date.accessioned2019-01-23T17:07:32Z
dc.date.available2019-01-23T17:07:32Z
dc.date.issued2019-01-18
dc.description.abstractEmpagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has shown remarkable reductions in cardiovascular mortality and heart failure admissions (EMPA-REG OUTCOME). However, the mechanism underlying the heart failure protective effects of empagliflozin remains largely unknown. Cardiac fibroblasts play an integral role in the progression of structural cardiac remodelling and heart failure, in part, by regulating extracellular matrix (ECM) homeostasis. Thus, in this study we sought to determine if empagliflozin has a direct effect on human cardiac fibroblast-mediated ECM remodelling. Empagliflozin attenuated myofibroblast activation as determined by collagen gel contraction and α-smooth muscle actin (α-SMA) characterization. Examination with confocal microscopy revealed cell morphology indicative of a quiescent phenotype and an attenuation of local ECM remodelling by these fibroblasts in response to empagliflozin. Furthermore, gene expression profiling indicated suppression of critical pro-fibrotic markers by empagliflozin. Taken together, we provide critical insights into the profound clinical benefits of empagliflozin on cardiac failure and mortality.en_US
dc.identifier.citationKang, S. (2019). The Role of Empagliflozin in Cardiac Fibroblast-Mediated Extracellular Matrix Remodeling (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/35757
dc.identifier.urihttp://hdl.handle.net/1880/109498
dc.language.isoenen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
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.en_US
dc.subjectFibroblasten_US
dc.subject.classificationMedicine and Surgeryen_US
dc.titleThe Role of Empagliflozin in Cardiac Fibroblast-Mediated Extracellular Matrix Remodelingen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Cardiovascular/Respiratory Scienceen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrue
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