The Role of Angiotensin-(1-7) in a Mouse Model of Renal Fibrosis

FieldValue
dc.contributor.authorZimmerman, Danielle
dc.date.accessioned2013-01-22T15:31:09Z
dc.date.available2013-01-22T15:31:09Z
dc.date.created2013
dc.date.issued2013
dc.identifier.urihttp://hdl.handle.net/10393/23692
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6410
dc.description.abstractAngiotensin-(1-7) [Ang-(1-7)] is a heptapeptide component of the renin angiotensin system and the endogenous ligand for the Mas receptor. Ang-(1-7) is generated mainly via angiotensin converting enzyme 2 (ACE2)-dependent cleavage of Angiotensin (Ang) II. Studies suggest Ang-(1-7) may protect against progression of renal injury in experimental models of chronic kidney disease, although the responses may be dose dependent. The role of Ang-(1-7) in the progression of renal fibrosis in unilateral ureteral obstruction (UUO) remains unclear. We tested the hypothesis that endogenous Ang-(1-7) and low dose exogenous Ang-(1-7) would protect against renal injury in the UUO model, while high dose Ang-(1-7) would exacerbate renal injury. Male C57Bl/6 mice underwent UUO and received vehicle, the Ang-(1-7) antagonist A779, or one of three doses of Ang-(1-7) for 10 days. Treatment with A779 exacerbated renal injury as seen by increased fibronectin, transforming growth factor-β (TGF-β), and α-smooth muscle actin (α-SMA) expression, increased tubulointerstitial fibrosis scores, macrophage infiltration, apoptosis, and NADPH oxidase activity in obstructed kidneys. Paradoxically, delivery of exogenous Ang-(1-7) was associated with increased renal injury regardless of dose. Taken together, these data indicate the Mas receptor may be sensitive to concentrations of Ang-(1-7) within the obstructed kidney and that exogenous Ang-(1-7) stimulates pro-fibrotic and pro-inflammatory signalling through unclear pathways.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectAngiotensin-(1-7)
dc.subjectrenal fibrosis
dc.subjectUUO
dc.subjectchronic kidney disease
dc.subjectA779
dc.subjectrenal inflammation
dc.titleThe Role of Angiotensin-(1-7) in a Mouse Model of Renal Fibrosis
dc.typeThesis
dc.faculty.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
dc.contributor.supervisorBurns, Kevin
dc.contributor.supervisorTouyz, Rhian
dc.embargo.termsimmediate
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
CollectionThèses, 2011 - // Theses, 2011 -

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