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Stimulation of the kinin B2 receptor has been previously reported to promote AAA development and rupture in a mouse model. The endogenous B2 receptor agonist, bradykinin, is generated from the kallikrein\u2013kinin system following activation of plasma kallikrein by Factor XII (FXII). In the current study whole-body FXII deletion, or neutralisation of activated FXII (FXIIa), inhibited expansion of the suprarenal aorta (SRA) of apolipoprotein E-deficient mice in response to angiotensin II (AngII) infusion. FXII deficiency or FXIIa neutralisation led to decreased aortic tumor necrosis factor-\u03b1-converting enzyme (TACE\/a disintegrin and metalloproteinase-17 (aka tumor necrosis factor-\u03b1-converting enzyme) (ADAM-17)) activity, plasma kallikrein concentration, and epithelial growth factor receptor (EGFR) phosphorylation compared with controls. FXII deficiency or neutralisation also reduced Akt1 and Erk1\/2 phosphorylation and decreased expression and levels of active matrix metalloproteinase (Mmp)-2 and Mmp-9. The findings suggest that FXII, kallikrein, ADAM-17, and EGFR are important molecular mediators by which AngII induces aneurysm in apolipoprotein E-deficient mice. This could be a novel pathway to target in the design of drugs to limit AAA progression.<\/jats:p>","DOI":"10.1042\/cs20191020","type":"journal-article","created":{"date-parts":[[2020,4,20]],"date-time":"2020-04-20T11:12:06Z","timestamp":1587381126000},"page":"1049-1061","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Factor XII blockade inhibits aortic dilatation in angiotensin II-infused apolipoprotein E-deficient mice"],"prefix":"10.1042","volume":"134","author":[{"given":"Corey\u00a0S.","family":"Moran","sequence":"first","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sai-Wang","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erik","family":"Biros","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smriti\u00a0M.","family":"Krishna","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan\u00a0K.","family":"Morton","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Kleinschnitz","sequence":"additional","affiliation":[{"name":"Department of Neurology, Essen University Hospital, Essen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Con","family":"Panousis","sequence":"additional","affiliation":[{"name":"Research and Development, CSL Limited, Parkville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-8848","authenticated-orcid":false,"given":"Jonathan","family":"Golledge","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, Australia"},{"name":"Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2020,5,4]]},"reference":[{"key":"2021113011115162800_B1","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/s41569-018-0114-9","article-title":"Abdominal aortic aneurysm: update on pathogenesis and medical treatments","volume":"16","author":"Golledge","year":"2019","journal-title":"Nat. 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