British journal of pharmacology · 2025
Fibrin induces infiltration of macrophages and neutrophils via integrin αMβ2 and triggers aortic dissection.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Li Jie, Zhang Jixiu, Zou Lingwei, Cao Meifang, Zhu Zhonghui, Yu Li, Zhou Min, Fu Weiguo, Dong Zhihui, Gao Huiyuan, Jiang Baohong
Аннотация
BACKGROUND AND PURPOSE: Infiltration 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 APPROACH: A model of AD was established in male mice using β-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 γ-chain knockout (Fgg+/-) mice were also used to evaluate the fibrin-integrin αMβ2 interaction.
KEY RESULTS: 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 αMβ2 was disclosed using protein-protein interaction analysis and immunofluorescence. The pivotal role of interactions between fibrin and integrin αMβ2 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 αMβ2 was also found in patients with AD.
CONCLUSION AND IMPLICATIONS: Fibrin plays a crucial role in triggering AD through recruiting macrophages and neutrophils via integrin αMβ2. Regulation of fibrin deposition or inhibition of the interaction between fibrin and integrin αMβ2 provide a potential therapy against AD.
EXPERIMENTAL APPROACH: A model of AD was established in male mice using β-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 γ-chain knockout (Fgg+/-) mice were also used to evaluate the fibrin-integrin αMβ2 interaction.
KEY RESULTS: 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 αMβ2 was disclosed using protein-protein interaction analysis and immunofluorescence. The pivotal role of interactions between fibrin and integrin αMβ2 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 αMβ2 was also found in patients with AD.
CONCLUSION AND IMPLICATIONS: Fibrin plays a crucial role in triggering AD through recruiting macrophages and neutrophils via integrin αMβ2. Regulation of fibrin deposition or inhibition of the interaction between fibrin and integrin αMβ2 provide a potential therapy against AD.