Exploratory research of novel management targeting Xa inhibitor for vascular diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08728
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Nagoya University
• Principal Investigator: BANNO Hiroshi 名古屋大学, 医学部附属病院, 講師 (80584721)
• Co-Investigator(Kenkyū-buntansha): 杉本 昌之 名古屋大学, 医学部附属病院, 病院講師 (00447814) ; 高橋 範子 名古屋大学, 医学部附属病院, その他 (10439177) ; 古森 公浩 名古屋大学, 医学系研究科, 教授 (40225587) ; 柴田 玲 名古屋大学, 医学系研究科, 特任教授 (70343689)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Xa阻害剤 / 動脈瘤 / 血管病

Outline of Final Research Achievements

Aneurysm model: Xa inhibitor was administered to mouse ascites-derived macrophages and gene expression analysis was performed. Apixaban administration suppressed MCP-1 expression, and edoxaban administration significantly increased TNF-α, IL-1b, IL-6, cathepsin K, and S gene expression. Therefore, apixaban and edoxaban were administered to the mouse aneurysm model, but the aneurysm-suppressing effect was not confirmed. On the contrary, anal bleeding was observed at all concentrations as a possible side effect.
Intimal hyperplasia model: A bypass model using the external jugular vein as a graft was created using rabbits. The intimal hyperplasia was evaluated by classifying into the edoxaban-administered group and the non-administered group, but no significant difference was observed between the two groups.

Free Research Field

心臓血管外科学

Academic Significance and Societal Importance of the Research Achievements

Xa阻害剤には抗凝固作用以外の多面的作用を有し，血管保護作用を発揮することが示唆される．本研究ではアピキサバン，エドキサバンによる動脈瘤形成および血管内膜肥厚の抑制，予防効果を期待して，検討を行ったが，残念ながらその効果は明らかではなかった．