{"id":{"repo_id":"uwo","oai_identifier":"oai:uwo.scholaris.ca:20.500.14721/38780"},"canonical_url":"https://search.dev.ndltd.org/etd/uwo/oai:uwo.scholaris.ca:20.500.14721/38780","repository":{"repo_id":"uwo","name":"Western University","base_url":"https://uwo.scholaris.ca/server/oai/request"},"display":{"title":"Effects of an Endothelial Cell-specific PAR2 Knockout on Endothelium-dependent and -independent Relaxation of Mouse Arteries","abstract":"Protease-activated receptor 2 (PAR2), a G-protein-coupled receptor expressed on endothelial cells (EC), is a target in chronic inflammatory diseases. Understanding the functions of EC PAR2 will inform the development of PAR2-based therapeutics to treat endothelial dysfunction, a characteristic of cardiovascular and metabolic diseases. In this thesis, we used isolated blood vessels from EC-specific PAR2 deficient mice (EC PAR2-/-) to investigate endothelium-dependent and -independent mechanisms of vascular smooth muscle relaxation. The findings indicate EC PAR2-/- mice exhibit reduced capacity for endothelium-dependent relaxation (EDR) of vascular smooth muscle in resistance-type arteries. Further, we found that treatment of mesenteric arteries with inhibitors of cyclooxygenase and nitric oxide synthase combined, restored normalized acetylcholine-induced EDR in EC PAR2-/- mice. Therefore, reduced EDR in EC PAR2-/- mesenteric arteries is associated with de novo cyclooxygenase activity. We conclude that EC PAR2-/- results in changes in vascular function, demonstrating its importance in regulating EDR mechanisms in resistance arteries.","abstract_html":"Protease-activated receptor 2 (PAR2), a G-protein-coupled receptor expressed on endothelial cells (EC), is a target in chronic inflammatory diseases. Understanding the functions of EC PAR2 will inform the development of PAR2-based therapeutics to treat endothelial dysfunction, a characteristic of cardiovascular and metabolic diseases. In this thesis, we used isolated blood vessels from EC-specific PAR2 deficient mice (EC PAR2-/-) to investigate endothelium-dependent and -independent mechanisms of vascular smooth muscle relaxation. The findings indicate EC PAR2-/- mice exhibit reduced capacity for endothelium-dependent relaxation (EDR) of vascular smooth muscle in resistance-type arteries. Further, we found that treatment of mesenteric arteries with inhibitors of cyclooxygenase and nitric oxide synthase combined, restored normalized acetylcholine-induced EDR in EC PAR2-/- mice. Therefore, reduced EDR in EC PAR2-/- mesenteric arteries is associated with de novo cyclooxygenase activity. We conclude that EC PAR2-/- results in changes in vascular function, demonstrating its importance in regulating EDR mechanisms in resistance arteries.","abstract_has_math":false,"creators":["Viola, Stephanie Alexis"],"institution":"The University of Western Ontario","degree_name":"M Sc","degree_level":null,"degree_discipline":"Physiology and Pharmacology","degree_department":null,"school":null,"contributors":[],"advisors":["McGuire, John J."],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-08-20","date_published":"2025-08-20","updated_at":"2026-07-27T21:56:20Z","subjects":["Protease-activated receptor 2 (PAR2)","endothelial dysfunction","endothelium-dependent relaxation","wire myography","mouse model"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://hdl.handle.net/20.500.14721/38780","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["McGuire, John J."]},{"key":"dc:creator","label":"Author","values":["Viola, Stephanie Alexis"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2025-09-03T19:08:44Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2025-09-03T19:08:44Z"]},{"key":"dc:date.issued","label":"Date","values":["2025-08-20"]},{"key":"dc:publisher","label":"Institution","values":["The University of Western Ontario"]},{"key":"dc:type","label":"Dc Type","values":["thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Physiology and Pharmacology"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M Sc"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Western Ontario"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Protease-activated receptor 2 (PAR2)","endothelial dysfunction","endothelium-dependent relaxation","wire myography","mouse model"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/20.500.14721/38780"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["This thesis is under embargo until August 31, 2027."]},{"key":"dc:description.abstract","label":"Abstract","values":["Protease-activated receptor 2 (PAR2), a G-protein-coupled receptor expressed on endothelial cells (EC), is a target in chronic inflammatory diseases. Understanding the functions of EC PAR2 will inform the development of PAR2-based therapeutics to treat endothelial dysfunction, a characteristic of cardiovascular and metabolic diseases. In this thesis, we used isolated blood vessels from EC-specific PAR2 deficient mice (EC PAR2-/-) to investigate endothelium-dependent and -independent mechanisms of vascular smooth muscle relaxation. The findings indicate EC PAR2-/- mice exhibit reduced capacity for endothelium-dependent relaxation (EDR) of vascular smooth muscle in resistance-type arteries. Further, we found that treatment of mesenteric arteries with inhibitors of cyclooxygenase and nitric oxide synthase combined, restored normalized acetylcholine-induced EDR in EC PAR2-/- mice. Therefore, reduced EDR in EC PAR2-/- mesenteric arteries is associated with de novo cyclooxygenase activity. We conclude that EC PAR2-/- results in changes in vascular function, demonstrating its importance in regulating EDR mechanisms in resistance arteries."]},{"key":"dc:title","label":"Title","values":["Effects of an Endothelial Cell-specific PAR2 Knockout on Endothelium-dependent and -independent Relaxation of Mouse Arteries"]}]}],"canonical_facts":{"dc:contributor.advisor":["McGuire, John J."],"dc:creator":["Viola, Stephanie Alexis"],"dc:date.accessioned":["2025-09-03T19:08:44Z"],"dc:date.available":["2025-09-03T19:08:44Z"],"dc:date.issued":["2025-08-20"],"dc:description":["This thesis is under embargo until August 31, 2027."],"dc:description.abstract":["Protease-activated receptor 2 (PAR2), a G-protein-coupled receptor expressed on endothelial cells (EC), is a target in chronic inflammatory diseases. Understanding the functions of EC PAR2 will inform the development of PAR2-based therapeutics to treat endothelial dysfunction, a characteristic of cardiovascular and metabolic diseases. In this thesis, we used isolated blood vessels from EC-specific PAR2 deficient mice (EC PAR2-/-) to investigate endothelium-dependent and -independent mechanisms of vascular smooth muscle relaxation. The findings indicate EC PAR2-/- mice exhibit reduced capacity for endothelium-dependent relaxation (EDR) of vascular smooth muscle in resistance-type arteries. Further, we found that treatment of mesenteric arteries with inhibitors of cyclooxygenase and nitric oxide synthase combined, restored normalized acetylcholine-induced EDR in EC PAR2-/- mice. Therefore, reduced EDR in EC PAR2-/- mesenteric arteries is associated with de novo cyclooxygenase activity. We conclude that EC PAR2-/- results in changes in vascular function, demonstrating its importance in regulating EDR mechanisms in resistance arteries."],"dc:identifier.uri":["https://hdl.handle.net/20.500.14721/38780"],"dc:language.iso":["en"],"dc:publisher":["The University of Western Ontario"],"dc:subject":["Protease-activated receptor 2 (PAR2)","endothelial dysfunction","endothelium-dependent relaxation","wire myography","mouse model"],"dc:title":["Effects of an Endothelial Cell-specific PAR2 Knockout on Endothelium-dependent and -independent Relaxation of Mouse Arteries"],"dc:type":["thesis"],"thesis:degree_discipline":["Physiology and Pharmacology"],"thesis:degree_name":["M Sc"],"thesis:institution_name":["The University of Western Ontario"]},"updated_at":"2026-07-27T21:56:20Z"}