Focal Adhesion Kinase Promotes the Progression of Aortic Aneurysm by Modulating Macrophage Behavior
Focal Adhesion Kinase Promotes the Progression of Aortic Aneurysm by Modulating Macrophage Behavior
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DOI：
10.1161/atvbaha.116.308542
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发表时间：
2017-01-01
影响因子：
8.7
通讯作者：
Hamano, Kimikazu
中科院分区：
文献类型：
--
作者：
Harada, Takasuke;Yoshimura, Koichi;Hamano, Kimikazu
目的：腹主动脉瘤（AAA）是一种危及生命的血管疾病，与持续炎症和细胞外基质降解有关。巨噬细胞介导的AAA进展的分子机制仍不清楚。方法和结果-我们发现局灶黏附激酶（FAK）的表达和活性在被招募到AAA组织的巨噬细胞中增强。FAK增强肿瘤坏死因子诱导的巨噬细胞分泌基质降解酶和趋化因子。FAK还能促进巨噬细胞趋化。在小鼠实验中，FAK抑制剂可以抑制局部巨噬细胞的积累，显著抑制化学诱导的AAA的发生和发展。结论：FAK在巨噬细胞行为中起关键作用，这是AAA慢性进展的基础。这些发现为AAA的进展提供了新的见解，并将FAK确定为新的治疗靶点。
Objective-Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease that is associated with persistent inflammation and extracellular matrix degradation. The molecular mechanisms underlying the macrophage-mediated progression of AAA remain largely unclear.Approach and Results-We show that focal adhesion kinase (FAK) expression and activity are enhanced in macrophages that are recruited to AAA tissue. FAK potentiates tumor necrosis factor-alpha-induced secretion of matrix-degrading enzymes and chemokines by cultured macrophages. FAK also promotes macrophage chemotaxis. In mice, the administration of a FAK inhibitor that tempers local macrophage accumulation markedly suppresses the development and progression of chemically induced AAA.Conclusions-FAK plays a key role in macrophage behavior, which underlies the chronic progression of AAA. These findings provide insights into AAA progression and identify FAK as a novel therapeutic target.