Basic research for critical limb ischemia therapy targeting TRPV4 by inducing angiogenesis and lymphangiogenesis

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18198
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Fukuoka University
• Principal Investigator: Hideaki Yamada 福岡大学, 医学部, 助教 (80785006)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: TRPV4 / リンパ管新生 / 血管新生 / 虚血肢 / 低酸素

Outline of Final Research Achievements

The purpose of this study was to establish a new angiogenic therapy to eliminate edema, which is a challenge in angiogenic therapy for critical limb ischemia. Lymphatic vessels have a crucial role for solving edema. We focused on TRPV4, which is expected to have angiogenic and lymphangiogenic effects, and conducted validation experiments using a mouse ischemic limb model to elucidate the following.
1) TRPV4 agonist improved the blood flow of ischemic hind limb by inducing angiogenesis and lymphangiogenesis; 2) excessive TRPV4 expression was detected on ischemic hind limb under hypoxic condition; 3) TRPV4 agonist can be expected to enhance this effect.
TRPV4-targeted therapy is a promising treatment for critical limb ischemia.

Free Research Field

心臓血管外科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、血管再生治療の弊害である浮腫を解決する新たな治療法の確立として期待できる。重症下肢虚血治療研究のみならず再生移植医学全般の治療研究への応用が期待できる。