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ID 114209
著者
Hara, Tomoya Tokushima University
Tanaka, Kimie The University of Tokyo
Higashikuni, Yasutomi The University of Tokyo
Hirata, Yoichiro The University of Tokyo
島袋, 充生 Tokushima University|Fukushima Medical University KAKEN研究者をさがす
キーワード
Macrophage
Neointima formation
Inflammation
Activated factor X
Rivaroxaban
資料タイプ
学術雑誌論文
抄録
Accumulating evidence suggests that activated factor X (FXa), a key coagulation factor, plays an important role in the development of vascular inflammation through activation of many cell types. Here, we investigated whether pharmacological blockade of FXa attenuates neointima formation after wire-mediated vascular injury. Transluminal femoral artery injury was induced in C57BL/6 mice by inserting a straight wire. Rivaroxaban (5 mg/kg/day), a direct FXa inhibitor, was administered from one week before surgery until killed. At four weeks after surgery, rivaroxaban significantly attenuated neointima formation in the injured arteries compared with control (P<0.01). Plasma lipid levels and blood pressure were similar between the rivaroxaban-treated group and non-treated group. Quantitative RT-PCR analyses demonstrated that rivaroxaban reduced the expression of inflammatory molecules (e.g., IL-1β and TNF-α) in injured arteries at seven days after surgery (P<0.05, respectively). In vitro experiments using mouse peritoneal macrophages demonstrated that FXa increased the expression of inflammatory molecules (e.g., IL-1β and TNF-α), which was blocked in the presence of rivaroxaban (P<0.05). Also, in vitro experiments using rat vascular smooth muscle cells (VSMC) demonstrated that FXa promoted both proliferation and migration of this cell type (P<0.05), which were blocked in the presence of rivaroxaban. Inhibition of FXa by rivaroxaban attenuates neointima formation after wire-mediated vascular injury through inhibition of inflammatory activation of macrophages and VSMC.
掲載誌名
European Journal of Pharmacology
ISSN
00142999
cat書誌ID
AA00639687
AA11527211
出版者
Elsevier
820
開始ページ
222
終了ページ
228
発行日
2017-12-18
権利情報
© 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
医学系