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Fibrin induces infiltration of macrophages and neutrophils via integrin αMβ2 and triggers aortic dissection

文献类型：期刊论文

作者Li, Jie1,2; Zhang, Jixiu2,7; Zou, Lingwei4,5,6; Cao, Meifang3; Zhu, Zhonghui1,2; Yu, Li1,2; Zhou, Min4,5,6; Fu, Weiguo4,5,6; Dong, Zhihui4,5,6; Gao, Huiyuan7
刊名BRITISH JOURNAL OF PHARMACOLOGY
出版日期2025-04-07
页码17
关键词aortic dissection fibrin integrin alphaMbeta2 macrophages neutrophils
ISSN号0007-1188
DOI10.1111/bph.70033
通讯作者Dong, Zhihui(dzh926@126.com) ; Gao, Huiyuan(sypugaohy@163.com) ; Jiang, Baohong(jiangbh@simm.ac.cn)
英文摘要Background and PurposeInfiltration of macrophages and neutrophils plays a crucial role in the occurrence of aortic dissection (AD), while the mechanism elucidating their infiltration remains unknown. The present study aimed to delineate the underlying mechanism and provide a potential therapeutic strategy to attenuate AD progression.Experimental ApproachA model of AD was established in male mice using beta-aminopropionitrile 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-lowering drugs and fibrinogen gamma-chain knockout (Fgg+/-) mice were also used to evaluate the fibrin-integrin alpha M beta 2 interaction.Key ResultsFibrin 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 alpha M beta 2 was disclosed using protein-protein interaction analysis and immunofluorescence. The pivotal role of interactions between fibrin and integrin alpha M beta 2 in AD progression was confirmed by cell adhesion in vitro, down-regulation of fibrin using batroxobin and Fgg+/- mice in vivo. The relevance of fibrin and integrin alpha M beta 2 was also found in patients with AD.Conclusion and ImplicationsFibrin plays a crucial role in triggering AD through recruiting macrophages and neutrophils via integrin alpha M beta 2. Regulation of fibrin deposition or inhibition of the interaction between fibrin and integrin alpha M beta 2 provide a potential therapy against AD.
WOS关键词CELL-ADHESION MOLECULES ; CONCISE GUIDE ; LEUKOCYTE ; INJURY ; ALPHA(M)BETA(2) ; RECOGNITION
资助项目Biological Resources Program, Chinese Academy of Sciences ; Zhao Guoping Academician Workstation (Hangzhou Academician Workstation) of Zhejiang Chinese Medical University
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:001460496200001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/316902]  
专题中国科学院上海药物研究所
通讯作者Dong, Zhihui; Gao, Huiyuan; Jiang, Baohong
作者单位1.Univ Chinese Acad Sci, Sch Pharm, Beijing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai, Peoples R China
3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing, Peoples R China
4.Natl Clin Res Ctr Intervent Med, Shanghai, Peoples R China
5.Fudan Univ, Inst Vasc Surg, Shanghai, Peoples R China
6.Fudan Univ, Zhongshan Hosp, Dept Vasc Surg, Shanghai, Peoples R China
7.Shenyang Pharmaceut Univ, Shenyang, Peoples R China
推荐引用方式
GB/T 7714		 Li, Jie,Zhang, Jixiu,Zou, Lingwei,et al. Fibrin induces infiltration of macrophages and neutrophils via integrin αMβ2 and triggers aortic dissection[J]. BRITISH JOURNAL OF PHARMACOLOGY,2025:17.
APA Li, Jie.,Zhang, Jixiu.,Zou, Lingwei.,Cao, Meifang.,Zhu, Zhonghui.,...&Jiang, Baohong.(2025).Fibrin induces infiltration of macrophages and neutrophils via integrin αMβ2 and triggers aortic dissection.BRITISH JOURNAL OF PHARMACOLOGY,17.
MLA Li, Jie,et al."Fibrin induces infiltration of macrophages and neutrophils via integrin αMβ2 and triggers aortic dissection".BRITISH JOURNAL OF PHARMACOLOGY (2025):17.

入库方式： OAI收割

来源：上海药物研究所

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