Identification and elucidating of function of cells involved with intimal hyperplasia in a valve site of vein graft

• Project/Area Number: 18K16380
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Asahikawa Medical College
• Principal Investigator: Kikuchi Shinsuke 旭川医科大学, 医学部, 助教 (80596297)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2018: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
• Keywords: 内膜肥厚 / 静脈グラフト / 重症虚血 / 末梢バイパス術 / グラフト不全 / 静脈弁 / 末梢動脈疾患 / 下肢動脈バイパス術 / 大伏在静脈 / 弁 / バイパス術 / 血行再建術 / 閉塞性動脈硬化症 / 自家静脈 / グラフト狭窄 / 下肢動脈疾患 / 重症虚血肢

Outline of Final Research Achievements

With spreading of lifestyle-related diseases, a number of peripheral artery disease (PAD) patients is increasing. As one of treatments for PAD, bypass surgery is very important for PAD patients with severe grade of atherosclerosis, which is difficult to treat by endovascular therapy. Bypass surgery using a vein graft is generally durable, however 20% of bypass grafts develop graft stenosis and graft thrombosis due to mainly intimal hyperplasia. In this study, elucidating of identification and function of cells involved with intimal hyperplasia at a venous valve site of vein graft, common site of graft stenosis. Especially, genetic changes of the cells and tissues are elucidated, and further study is needed to establish as clinical application for overcoming the clinical issues by regulating the genetic changes of cells.

Academic Significance and Societal Importance of the Research Achievements

末梢動脈疾患に対する外科的血行再建では、大伏在静脈を用いることが多い。しかし、20-30％の割合で、グラフト狭窄を生じ、閉塞に至ってしまう点が臨床上の問題である。本研究課題では、下肢動脈再建に用いられる大伏在静脈におけるグラフト狭窄の原因を同定することを目的としており、前回の若手研究結果から大伏在静脈の弁部にグラフト狭窄と関連するターゲットが存在することを証明した。
静脈グラフトを用いた外科的血行再建は、カテーテル治療が発達する時代でも一定の役割をもつため、グラフト不全の原因となる内膜肥厚の制御により、その治療耐久性は飛躍的に向上することを背景に研究している。

Research Products

• [Int'l Joint Research] ワシントン大学(米国)
• [Int'l Joint Research] University of Washington/Benaroya Research Institute/Virginia Mason Medical Center(米国)
• [Int'l Joint Research] ワシントン大学血管外科(米国)
• [Journal Article] Predictive Model for Postoperative Ambulatory Function after Lower Extremity Bypass in Chronic Limb-Threatening Ischemia (2021)
  • Author(s): Keisuke Miyake, Shinsuke Kikuchi, Takamitsu Tatsukawa, Daiki Uchida, Atsuhiro Koya, Yoshiki Sawa, Nobuyoshi Azuma
  • Journal Title: Ann Vasc Surg . Volume: 71 Pages: 321-330
  • DOI: 10.1016/j.avsg.2020.07.033
  • Peer Reviewed
• [Journal Article] <i>NT5E</i> Genetic Mutation Is a Rare But Important Cause of Intermittent Claudication and Chronic Limb-Threatening Ischemia (2020)
  • Author(s): Azuma N, Uchida T, Kikuchi S, Sadahiro M, Shintani T, Yanagi K, Higashita R, Yamashita A, Makita Y, Kaname T.
  • Journal Title: Circulation Journal Volume: 84 Issue: 7 Pages: 1183-1188
  • DOI: 10.1253/circj.CJ-20-0153
  • NAID: 130007864270
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2020-06-25
  • Peer Reviewed / Open Access
• [Journal Article] Inhibitory Effects of PRG4 on Migration and Proliferation of Human Venous Cells (2020)
  • Author(s): Lei Wang, Shinsuke Kikuchi, Tannin A Schmidt, Max Hoofnagle, Thomas N Wight, Nobuyoshi Azuma, Gale L Tang, Michael Sobel, Gautum R Velamoor, Nahush A Mokadam, Richard D Kenagy
  • Journal Title: J Surg Res . Volume: 253 Pages: 53-62
  • DOI: 10.1016/j.jss.2020.03.028
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Extracellular Vesicles Are Key Regulators of Tumor Neovasculature (2020)
  • Author(s): Naoya Kuriyama, Yusuke Yoshioka, Shinsuke Kikuchi, Nobuyoshi Azuma, Takahiro Ochiya
  • Journal Title: Front Cell Dev Biol . Volume: 8 Pages: 611039-611039
  • DOI: 10.3389/fcell.2020.611039
  • Peer Reviewed / Open Access
• [Journal Article] Collateral artery bypass in the infrapopliteal segment (2020)
  • Author(s): Tochikubo A, Koya A, Uchida D, Tada Y, Kikuchi S, Azuma N.
  • Journal Title: J Vasc Surg Cases Innov Tech . Volume: 7 Issue: 1 Pages: 30-34
  • DOI: 10.1016/j.jvscit.2020.12.003
  • Peer Reviewed / Open Access
• [Journal Article] Development of gene therapy with a cyclic adenosine monophosphate response element decoy oligodeoxynucleotide to prevent vascular intimal hyperplasia (2020)
  • Author(s): Uchida Daiki、Saito Yukihiro、Kikuchi Shinsuke、Yoshida Yuri、Hirata Satoshi、Sasajima Tadahiro、Azuma Nobuyoshi
  • Journal Title: Journal of Vascular Surgery Volume: 71 Issue: 1 Pages: 229-241
  • DOI: 10.1016/j.jvs.2019.02.042
  • Peer Reviewed
• [Journal Article] Involvement of Extracellular Vesicles in Vascular-Related Functions in Cancer Progression and Metastasis (2019)
  • Author(s): Kikuchi Shinsuke、Yoshioka Yusuke、Prieto-Vila Marta、Ochiya Takahiro
  • Journal Title: International Journal of Molecular Sciences Volume: 20 Issue: 10 Pages: 2584-2584
  • DOI: 10.3390/ijms20102584
  • Peer Reviewed
• [Journal Article] Effectiveness and Safety of Ultrasound Guided Lower Extremity Nerve Blockade in Infragenicular Bypass Grafting for High Risk Patients With Chronic Limb Threatening Ischaemia (2019)
  • Author(s): Kikuchi Shinsuke、Yamaguchi Takuya、Miyake Keisuke、Uchida Daiki、Koya Atsuhiro、Iida Takafumi、Kurosawa Atsushi、Sasakawa Tomoki、Kunisawa Takayuki、Azuma Nobuyoshi
  • Journal Title: European Journal of Vascular and Endovascular Surgery Volume: 58 Issue: 2 Pages: 206-213
  • DOI: 10.1016/j.ejvs.2019.03.023
  • NAID: 40022289507
  • Peer Reviewed
• [Presentation] Factors Related to Postoperative Delirium in Vascular Surgery in an Aging Society (2020)
  • Author(s): A. Tochikubo, S. Kikuchi, K. Takahashi, T. Tatsukawa, Y. Yoshida, D. Uchida, A. Koya, N. Azuma
  • Organizer: 34th ESVS Annual Meeting
  • Int'l Joint Research
• [Presentation] Possibility of >> Exosomal MicroRNAs Associated with Chronic Limb-Threatening Ischemia as a >> promising Biomarker (2020)
  • Author(s): Shinsuke Kikuchi, Yusuke Yoshioka, Naoya Kuriyama, Yuri Yoshida, Kurataka Otsuka, Yusuke Yamamoto, Nobuyoshi Azuma, Takahiro Ochiya
  • Organizer: International Society for Extracellular Vesicles 2020
  • Int'l Joint Research
• [Presentation] Develpment of a biomarker for peripheral artery disease using extracellular vesicles associated miRNA (2020)
  • Author(s): Naoya Kuriyama, Yusuke Yoshioka, Shinsuke Kikuchi, Nobuyoshi Azuma, Takahiro Ochiya
  • Organizer: International Society for Extracellular Vesicles 2021
  • Int'l Joint Research
• [Presentation] Significance of Recovery of Limb Function after surgical revascularization in Chronic Limb-Threatening Ischemia (2020)
  • Author(s): Kikuchi S, Uchida D, Kuriyama N, Takahashi K, Kamada K, Tatsukawa T, Tochikubo A, Yoshida Y, Koya A, Azuma N
  • Organizer: 2020 Vascular Annual Meeting
  • Int'l Joint Research
• [Presentation] Prognostic Factors of Long-term Survivors After Surgical Revascularization in Dialysis-dependent Patients with Chronic Limb Threatening Ischemia (2019)
  • Author(s): Shinsuke Kikuchi, Naoya Kuriyama, Ai Tochikubo, Daiki Uchida, Atsuhiro Koya, Tadahiro Sasajima, Nobuyoshi Azuma
  • Organizer: ESVS Annual Meeting 2019
  • Int'l Joint Research
• [Presentation] A Change of Duplex Sonographic Velocities and Flow of Infrapopliteal Vein Graft in 30 Days After Surgery is a Strong Predictor for 1-year Graft Patency (2019)
  • Author(s): Naoya Kuriyama, Shinsuke Kikuchi, Takamitsu Tatsukawa, Ai Tochikubo, Daiki Uchida, Atsuhiro Koya, Nobuyoshi Azuma
  • Organizer: ESVS Annual Meeting 2019
  • Int'l Joint Research