演題

IS-1-6

Role of focal adhesion kinase in abdominal aortic aneurysm

[演者] 原田 剛佑:1
[著者] 山下 修:1, 上田 晃志郎:1, 森景 則保:1, 吉村 耕一:1, 濱野 公一:1
1:山口大学器官病態外科

Background and aim: Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation, which contributes to the pathological remodeling of extracellular matrix. Focal adhesion kinase (FAK) is a key mediator of interactions of cells with the extracellular matrix, and has been suggested to regulate remodeling of extracellular matrix. The aim of this study was to elucidate the role of FAK in the pathogenesis of AAA. Methods and results: First, we observed significant increases in active form of FAK (pFAK) in human AAA walls, associated with inflammatory cell infiltration and destruction of elastic fibers. Next, we created the CaCl2-induced AAA model in mice, and found that the level of pFAK in the aorta continued to increase in the degenerative media at 28 and 42 days after CaCl2 treatment during AAA development. Furthermore, we applied FAK inhibitor PF573228 in human AAA tissues in ex vivo culture. Interestingly, inhibition of FAK caused a significant reduction in the activation level of c-Jun N-terminal kinase (JNK), a pro-inflammatory signaling molecule and also reduced the secretion of monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) in human AAA tissues.Conclusion: Our findings indicate that FAK has an important role in the pathogenesis of AAA and represents a potential therapeutic target for AAA.
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