Investigation of molecules regulating angiogenesis and thrombus formation

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K18435
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Shinshu University
• Principal Investigator: Hosomi Kento 信州大学, 医学部, 特任助教 (90793787)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 血管新生 / 血栓形成

Outline of Final Research Achievements

The aim of this study is to elucidate the solution of clinical problems in plastic surgery caused by blood vessels, which means to uncover how to regulate both angiogenesis and thrombus formation to survive transplanted flaps. Our focus point is a certain molecule that may provide a common basis for angiogenesis and thrombus formation. We utilized a mice model with an ischemic flap and compared the survival rate and the vascularization of the flap between wild type mice and transgenic mice. On postoperative days three and five, the survival rate and the vascularization of the flap were significantly lower in a transgenic mouse group. We analyzed blood samples from patients with vascular malformations. Patients with venous malformations had higher levels of D-dimer (mean 5.64 μg/mL), and blood levels of a candidate molecule was not significantly different compared to healthy subjects (n=13).

Free Research Field

再建外科

Academic Significance and Societal Importance of the Research Achievements

外傷、腫瘍切除、先天性疾患等により欠損した組織を補填するために行われる組織移植では、血流確保、すなわち血管新生確保と血栓形成防止が不可欠である。これらは別々の視点で捉えられてきたが、我々はその両方を同時に制御し、基盤となるメカニズム解明を目指した。それにより組織移植時のバイオマーカーの確立、特定の受容体を標的とした薬剤開発等につながると期待されるためである。本研究の虚血皮弁モデルでは、想定した分子が血管新生促進的に機能する可能性が示唆され、血管奇形患者血液では血栓形成への関与は不明だった。今後、同マウスモデルやヒトの相当する病態で新生血管と血栓形成および疼痛との関係について解析を行いたい。