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Issues Mol. Biol.","CIMB"],"abstract":"<jats:p>Proteinase-activated receptor 2 is a G protein-coupled receptor that regulates vascular tone and inflammatory signalling in the circulatory system. The roles of PAR2 appear complex and sometimes opposing. Studies using PAR2-deficient mice provide a framework to define these effects at the system level. This review examines cardiovascular phenotypes associated with PAR2 deficiency in basal conditions and in disease. PAR2 deficiency produces modest increases in arterial blood pressure and vascular stiffness while preserving endothelial vasodilator function. Cardiac function remains largely normal in young PAR2-deficient animals but changes with age. Older PAR2-deficient mice develop diastolic dysfunction and cardiac fibrosis. In disease models, PAR2 deficiency has been associated with increased fibrosis in cardiac and vascular tissues and reduced vascular inflammation in atherosclerosis. PAR2 deficiency is also associated with reduced plaque progression and features of plaque stabilisation. In myocardial ischaemia models, PAR2 deficiency has been associated with reduced cardiac injury and adverse remodelling. The effects of PAR2 deficiency on inflammatory signalling vary according to tissue and disease context. Together, these findings suggest that the cardiovascular consequences of PAR2 deficiency depend on physiological and pathological context. Future studies should define cell-specific mechanisms to guide therapeutic targeting of PAR2.<\/jats:p>","DOI":"10.3390\/cimb48080821","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:53:48Z","timestamp":1786539228000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteinase-Activated Receptor 2 (PAR2) Deficiency and Cardiovascular Regulation: Context-Dependent Effects on Inflammation and Fibrosis"],"prefix":"10.3390","volume":"48","author":[{"given":"Stephanie A.","family":"Viola","sequence":"first","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahnaz","family":"Siddiqua","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8716-9226","authenticated-orcid":false,"given":"Jesutofunmi","family":"Adesuyi","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5428-4499","authenticated-orcid":false,"given":"Yebin","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryia","family":"Ryskina","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0302-3884","authenticated-orcid":false,"given":"John J.","family":"McGuire","sequence":"additional","affiliation":[{"name":"Department of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"},{"name":"Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON N6A 5C1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5315","DOI":"10.4049\/jimmunol.169.9.5315","article-title":"Protease-Activated Receptor 2 Mediates Eosinophil Infiltration and Hyperreactivity in Allergic Inflammation of the Airway","volume":"169","author":"Schmidlin","year":"2002","journal-title":"J. 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