日本薬理学会年会要旨集
Online ISSN : 2435-4953
第92回日本薬理学会年会
セッションID: 92_2-O-30
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一般演題(口頭)
血管平滑筋細胞におけるプロテイナーゼ活性化型受容体1を介した凝固第FXI因子の細胞作用
*平野 勝也劉 文華橋本 剛山下 哲生
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会議録・要旨集 オープンアクセス

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Objectives: Coagulation factor XI (FXI) was reported to contribute to atherogenesis. The underlying mechanism remains unknown. We investigated the cellular effect of FXI and its mechanism in vascular smooth muscle cells.

Methods and main results: Activated FXI (FXIa) induced intracellular Ca2+ signaling mainly due to Ca2+ influx in the fura-2-loaded A7r5 cells, rat embryonic aorta smooth muscle cells. Pharmacological inhibitor (diltiazem) and genetic knockdown of L-type Ca2+ channel abolished the FXIa-induced Ca2+ influx. FXIa-induced Ca2+ signaling was abolished by atopaxar, a PAR1 antagonist. FXIa, when pre-incubated with a proteinase inhibitor p-APMSF, failed to elicit Ca2+ signaling in A7r5 cells. FXIa failed to induce Ca2+ signal in embryonic fibroblasts derived from PAR1-knockout mice. In vitro digestion assay revealed that FXIa cleaved the extracellular domain of PAR1 at the same site that thrombin cleaved. FXIa accelerated cell migration of A7r5 cells in a wound healing assay. The acceleration of cell migration was partly inhibited by atopaxar and diltiazem.

Conclusions: We provides the first evidence that FXIa exerts cellular effect via PAR1 in vascular smooth muscle cells.

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