Rivaroxaban, a specific FXa inhibitor, improved endothelium-dependent relaxation of aortic segments in diabetic mice

• Material Type: 博士論文
• Title: Rivaroxaban, a specific FXa inhibitor, improved endothelium-dependent relaxation of aortic segments in diabetic mice
• Volume: 9
• Author/Editor: Pham, Tran Phuong; Fukuda, Daiju; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Shimabukuro, Michio; Sata, Masataka
• Author Heading: Pham, Tran Phuong; Fukuda, Daiju; Yagi, Shusuke; Kusunose, Kenya; Yamada, Hirotsugu; Soeki, Takeshi; Shimabukuro, Michio; Sata, Masataka
• Publication, Distribution, etc.: Springer Nature
• Publication Date: 2019-08-01
• Publication Date (W3CDTF): 2019-08-01
• Alternative Title: 特異的活性化第X因子阻害薬であるリバーロキサバンは、糖尿病マウス大動脈の血管内皮依存性弛緩反応を改善した
• Periodical title: Scientific Reports
• Degree grantor/type: 徳島大学
• Date Granted: 2020-09-10
• Date Granted (W3CDTF): 2020-09-10
• Dissertation Number: 甲第3432号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第3432号
• Text Language Code: eng
• Subject Heading: Rivaroxaban; FXa; PAR2; Endothelial dysfunction
• Target Audience: 一般
• Note (General): Activated factor X (FXa) plays a central role in the coagulation cascade, while it also mediates vascular function through activation of protease-activated receptors (PARs). Here, we examined whether inhibition of FXa by rivaroxaban, a direct FXa inhibitor, attenuates endothelial dysfunction in streptozotocin (STZ)-induced diabetic mice. Induction of diabetes increased the expression of a major FXa receptor, PAR2, in the aorta (P < 0.05). Administration of rivaroxaban (10 mg/kg/day) to diabetic wild-type (WT) mice for 3 weeks attenuated endothelial dysfunction as determined by acetylcholine-dependent vasodilation compared with the control (P < 0.001), without alteration of blood glucose level. Rivaroxaban promoted eNOSSer1177 phosphorylation in the aorta (P < 0.001). Induction of diabetes to PAR2-deficient (PAR2−/−) mice did not affect endothelial function and eNOSSer1177 phosphorylation in the aorta compared with non-diabetic PAR2−/− mice. FXa or a PAR2 agonist significantly impaired endothelial function in aortic rings obtained from WT mice, but not in those from PAR2−/− mice. FXa promoted JNK phosphorylation (P < 0.01) and reduced eNOSSer1177 phosphorylation (P < 0.05) in human coronary artery endothelial cells (HCAEC). FXa-induced endothelial dysfunction in aortic rings (P < 0.001) and eNOSSer1177 phosphorylation (P < 0.05) in HCAEC were partially ameliorated by a JNK inhibitor. Rivaroxaban ameliorated diabetes-induced endothelial dysfunction. Our results suggest that FXa or PAR2 is a potential therapeutic target.
• DOI: info:doi/10.1038/s41598-019-47474-0; https://doi.org/info:doi/10.1038/s41598-019-47474-0
• Persistent ID (NDL): info:ndljp/pid/11551462; https://dl.ndl.go.jp/pid/11551462
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-10-06T21:18:06+09:00
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/114192
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp