Effects of an Endothelial Cell-specific PAR2 Knockout on Endothelium-dependent and -independent Relaxation of Mouse Arteries

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.

Name thesis:degree_name

M Sc

Discipline thesis:degree_discipline

Physiology and Pharmacology

Grantor dc:publisher

The University of Western Ontario

Year dc:date.issued

2025

Author dc:creator

• Viola, Stephanie Alexis

Advisor dc:contributor.advisor

• McGuire, John J.

• Protease-activated receptor 2 (PAR2)
• endothelial dysfunction
• endothelium-dependent relaxation
• wire myography
• mouse model

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/20.500.14721/38780

OAI identifier oai:identifier

oai:uwo.scholaris.ca:20.500.14721/38780