Clinical study for biomarker predicting vein graft intimal hyperplasia

• Project/Area Number: 26293309
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Asahikawa Medical College
• Principal Investigator: AZUMA NOBUYOSHI 旭川医科大学, 医学部, 教授 (30250559)
• Co-Investigator(Kenkyū-buntansha): 内田 大貴 旭川医科大学, 医学部, 助教 (80422038)
• Project Period (FY): 2014-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥15,210,000 (Direct Cost: ¥11,700,000、Indirect Cost: ¥3,510,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000); Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000); Fiscal Year 2014: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
• Keywords: 下肢閉塞性動脈硬化症 / 下肢血行再建 / 静脈グラフト狭窄 / 内膜肥厚 / バイオマーカー / マイクロRNA / 酸化ストレス / エクソソーム / 静脈グラフト / 末梢動脈血行再建 / 静脈グラフト閉塞 / 生活習慣病 / 末梢動脈疾患 / 重症下肢虚血 / 末梢動脈バイパス / グラフト狭窄 / 動脈硬化症 / 参加ストレス / 末梢動脈バイパス術 / 静脈グラフト内膜肥厚 / 静脈内皮機能 / 炎症性ストレス / バイパス手術

Outline of Final Research Achievements

A prospective observational study enrolled 120 vein bypass grafts in patients with critical limb ischemia was done in order to explore some biomarkers predicting the graft stenosis or occlusion. Preoperative oxidative stress marker (d-ROMs), heart failure, and female gender were listed as preoperative factors predicting vein graft failure. We also found some microRNAs extracted from exosome possibly predicting graft failure as results of next generation sequencer analysis.
Combinations of these preoperative factors may contribute to prediction of graft prognosis which may provide clinicians important suggestions for adequate treatment selection.

Academic Significance and Societal Importance of the Research Achievements

静脈グラフトの進行性内膜肥厚はおよそ２５%程度の症例に発生するとされているが、どの症例に発生するのか未だ明らかではなく、的確なグラフト予後予測が困難な状況である。今回の研究によって、いくつかのグラフト予後予測因子が明らかとなったことで、これらを適切に組み合わせて用いて術前に静脈グラフトを移植した場合の予後を予測できるようになれば、予後不良と予測された症例には別の治療法を選択するなど適切な治療方法の提示が可能となり、患者にも医療コストにも大いに意義がある。
さらに内膜肥厚の発生予測は他の血管治療にも応用可能であり、動脈硬化発生や再狭窄予防などの分野においても学術的価値も高いと考える。

Research Products

• [Journal Article] Development of the gene therapy with a CRE decoy ODN to prevent vascular intimal hyperplasia (2019)
  • Author(s): Daiki Uchida, Yukihiro Saito, Nobuyoshi Azuma, et al.
  • Journal Title: Journal of Vascular Surgery Volume: in press
  • Peer Reviewed
• [Journal Article] Evaluation of paramalleolar and inframalleolar bypasses in dialysis- and nondialysis- dependent patients with critical limb ischemia (2018)
  • Author(s): Shinsuke Kikuchi, Tadahiro Sasajima, Nobuyoshi Azuma, et al.
  • Journal Title: Journal of Vascular Surgery Volume: 67 Pages: 826-837
  • NAID: 40021632096
  • Peer Reviewed
• [Journal Article] Evaluation of paramalleolar and inframalleolar bypasses in dialysis- and nondialysis-dependent patients with critical limb ischemia. (2018)
  • Author(s): Kikuchi S, Sasajima T, Inaba M, Uchida D, Kokubo T, Saito Y, Koya A, Uchida H, Azuma N
  • Journal Title: Journal of vascular surgery Volume: 67(3) Issue: 3 Pages: 826-837
  • DOI: 10.1016/j.jvs.2017.07.116
  • NAID: 40021632096
  • Peer Reviewed / Open Access
• [Journal Article] Recent Progress of Bypass Surgery to the Dialysis-Dependent Patients with Critical Limb Ischemia (2017)
  • Author(s): Nobuyoshi Azuma,Shinsuke Kikuchi,Hiroko Okuda,Keisuke Miyake,Atsuhiro Koya
  • Journal Title: Annals of Vascular Diseases Volume: 10 Issue: 3 Pages: 178-184
  • DOI: 10.3400/avd.ra.17-00076
  • NAID: 130006099984
  • ISSN: 1881-641X, 1881-6428
  • Peer Reviewed / Open Access
• [Presentation] Development of the Gene Therapy With CRE Decoy ODN to Prevent Vascular Intimal Hyperplasia (2018)
  • Author(s): Daiki Uchida, Yukihiro Saito, Nobuyoshi Azuma
  • Organizer: American Heart Association ATVB/PVD 2018 Meeting
  • Int'l Joint Research
• [Presentation] Gender difference of distal bypass graft patency:relationship between preoperatove foot infection and graft stenosis (2018)
  • Author(s): Hitoko Okuda,Atsuhiro Koya,Keisuke Miyake,Shinsuke Kikuchi and Nobuyoshi Azuma
  • Organizer: 第46回日本血管外科学会
  • Int'l Joint Research
• [Presentation] Predictive Equation of Graft Flow in Distal Bypass Grafting in Critical Limb Ischemia (2017)
  • Author(s): Keisuke Miyake, MD, Shinsuke Kikuchi, MD, Hiroko Okuda, MD, Atsuhiro Koya, MD, Nobuyoshi Azuma , MD
  • Organizer: 2017 Vascular Annual Meeting San Diego
  • Int'l Joint Research
• [Presentation] GENDER-RELATED DIFFERENCES OF VEIN BYPASS GRAFT INTIMAL HYPERPLASIA AND CLINICAL OUTCOMES FOR CRITICAL LIMB ISCHEMIA;A PROPENSITY MATCHED ANALYSIS (2017)
  • Author(s): Hiroko Okuda,Shinsuke Kikuchi,Keisuke Miyake,Atsuhiro Koya,Yukihiro Saito,Nobuyosi Azuma
  • Organizer: The European Society for Vascular Surgery 31st Annual Meeting
  • Int'l Joint Research
• [Presentation] Involvement of hemodialysis to intimal hyperplasia development in paramalleolar bypass vein grafts (2016)
  • Author(s): Kikuchi S, Sasajima T, Uchida D, Koya A, Azuma N.
  • Organizer: Society for Vascular Surgery
  • Place of Presentation: Washintong DC, U.S.A.
  • Year and Date: 2016-06-09
  • Int'l Joint Research
• [Remarks] 基礎研究血管・呼吸・腫瘍病態外科学分野のご案内
  • URL: https://www.asahikawa-med-surgery.jp/study/kiso-01
• [Remarks] 循環・呼吸・腫瘍病態外科学分野基礎研究のご紹介
  • URL: https://www.asahikawa-med-surgery.jp/study/kiso-01
• [Remarks] 旭川医科大学循環・呼吸・腫瘍病態外科学学分野ホームページ上
  • URL: http://www.asahikawa-med.ac.jp/index.php?f=facilities_guide+rinsyoigaku_jks_out