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The present study aimed to delineate the underlying mechanism and provide a potential therapeutic strategy to attenuate AD progression.<\/jats:p><\/jats:sec>Experimental Approach<\/jats:title>A model of AD was established in male mice using \u03b2<\/jats:italic>\u2010aminopropionitrile and angiotensin II. Proteomic analysis, histological evaluation, flow cytometry, western blot, multiple fluorescence staining and adhesion assays were used to evaluate fibrin and inflammatory cells during AD progression. Fibrinogen\u2010lowering drugs and fibrinogen \u03b3<\/jats:italic>\u2010chain knockout (Fgg+\/\u2212<\/jats:sup>) mice were also used to evaluate the fibrin\u2010integrin \u03b1<\/jats:italic>M\u03b2<\/jats:italic>2 interaction.<\/jats:p><\/jats:sec>Key Results<\/jats:title>Fibrin deposition was confirmed by proteomic analysis and histological staining, accompanied by infiltration of macrophages and neutrophils detected by flow cytometry during the progression of AD. After confirming that macrophages and neutrophils infiltrated at the sites where fibrin was deposited by immunofluorescence, an association between fibrin and the integrin \u03b1<\/jats:italic>M\u03b2<\/jats:italic>2 was disclosed using protein\u2013protein interaction analysis and immunofluorescence. The pivotal role of interactions between fibrin and integrin \u03b1<\/jats:italic>M\u03b2<\/jats:italic>2 in AD progression was confirmed by cell adhesion in vitro, down\u2010regulation of fibrin using batroxobin and Fgg+\/\u2212<\/jats:sup> mice in vivo. The relevance of fibrin and integrin \u03b1<\/jats:italic>M\u03b2<\/jats:italic>2 was also found in patients with AD.<\/jats:p><\/jats:sec>Conclusion and Implications<\/jats:title>Fibrin plays a crucial role in triggering AD through recruiting macrophages and neutrophils via integrin \u03b1<\/jats:italic>M\u03b2<\/jats:italic>2. Regulation of fibrin deposition or inhibition of the interaction between fibrin and integrin \u03b1<\/jats:italic>M\u03b2<\/jats:italic>2 provide a potential therapy against AD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70033","type":"journal-article","created":{"date-parts":[[2025,4,8]],"date-time":"2025-04-08T00:14:23Z","timestamp":1744071263000},"page":"3577-3593","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Fibrin induces infiltration of macrophages and neutrophils via integrin \u03b1<\/i>M\u03b2<\/i>2 and triggers aortic dissection"],"prefix":"10.1111","volume":"182","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"},{"name":"School of Pharmacy University of Chinese Academy of Sciences Beijing 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