Clinical study of stem cell function in patients with peripheral arterial disease: Role of stem cell senescence in poor prognosis of patients.

• Project/Area Number: 18K08749
• 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: Asahikawa Medical College
• Principal Investigator: Nobuyoshi Azuma 旭川医科大学, 医学部, 教授 (30250559)
• Co-Investigator(Kenkyū-buntansha): 菊地 信介 旭川医科大学, 医学部, 助教 (80596297) ; 吉田 有里 旭川医科大学, 大学病院, 助教 (50646057)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 下肢閉塞性動脈硬化症 / 生命予後 / 幹細胞機能 / マイクロRNA / 生活習慣病 / 酸化ストレス / 末梢動脈疾患 / 血管内皮前駆細胞 / 血行再建

Outline of Final Research Achievements

To understand mechanisms why peripheral artery disease (PAD) is associated with poor prognosis, we collected blood samples from patients with chronic limb-threatening ischemia(CLTI) before revascularization, then those CLTI patients were observed thereafter. Regarding prognosis after revascularization, we selected four patients who died within 1year after bypass surgery and another 4 patients who are surviving more than 2 years were selected. Then we performed microarray of microRNAs (miRNAs) using the preserved blood sample took before bypass surgery. As the results, 14 species of unknown miRNAs negatively associated patient’s prognosis and 3 species of unknown miRNA positively associated the prognosis. We will continue this study to find out miRNAs function, which might contribute to understand why PAD is so strong predictor of poor prognosis.

Academic Significance and Societal Importance of the Research Achievements

PADは、冠動脈疾患(CAD)や脳血管疾患(CVD)と並んで3大動脈硬化性疾患の柱であるが、PADはCADやCVDとの合併頻度が高く、かつ、PADが最も生命予後が不良であることが知られている。さらに、PADが合併するとCADやCVDの予後が著しく不良になることも知られている。本研究で生命予後に関与する可能性のあるmiRNAの機能が解明され、幹細胞との関係性が明らかになれば、PADがどのような機序で予後不良を招いているのか理解が深まると期待される。さらに、血行再建後の再狭窄にもmiRNAが関連しているのであれば、血管再生能や修復能の改善ひいては生命予後改善への介入研究につながることを期待する。

Research Products

• [Journal Article] Predictive Model for Mortality Risk Including the Wound, Ischemia, Foot Infection Classification in Patients Undergoing Revascularization for Critical Limb Ischemia (2019)
  • Author(s): Azuma N, Takahara M, Kodama A, Soga Y, Terashi H, Tazaki J, Yamaoka T, Koya A, Iida O
  • Journal Title: Circulation. Cardiovascular interventions. Volume: 12 Issue: 12
  • DOI: 10.1161/circinterventions.119.008015
  • Peer Reviewed
• [Presentation] Development of a biomarker for peripheral artery disease using extracellular vesicles associated miRNA (2021)
  • Author(s): 栗山直也、吉岡祐亮、菊地信介、東信良、落谷孝広
  • Organizer: International Society for Extracellular Vesicles 2021
  • Int'l Joint Research
• [Presentation] 末梢動脈疾患による重症下肢虚血におけるExsomal microRNA 発現プロファイルから見たリキッドバイオプシーの可能性 (2020)
  • Author(s): 菊地信介、吉岡祐亮、大塚蔵嵩、山本雄介、東信良、落谷孝広
  • Organizer: 第4回Liquid Biopsy 研究会
• [Presentation] Possibility of Exosomal MicroRNAs Associated with Chronic Limb-Threatening Ischemia as a promising Biomarker (2020)
  • Author(s): 菊地信介、吉岡祐亮、栗山直也、吉田有里、大塚蔵嵩、山本雄介、東信良、落谷孝広
  • Organizer: International Society for Extracellular Vesicles 2020
  • Int'l Joint Research
• [Presentation] 末梢動脈疾患による重症下肢虚血におけるExosomal microRNAによるスクリーニグモダリティとしての可能性 (2020)
  • Author(s): 菊地信介、吉岡祐亮、栗山直也、吉田有里、東信良、落谷孝広
  • Organizer: 第7回日本細胞外小胞学会
• [Presentation] Pre-operative d-ROMs as a biomarker for predicting graft failure after distal bypass surgery in CLTI patients (2020)
  • Author(s): Daiki.U，Kikuchi S, Uchida D, Kuriyama N, Takahashi K, Kamada K, Tatsukawa T, Tochikubo A, Yoshida Y, Koya A, Azuma N
  • Organizer: SVS 2020 Vascular Annual Meeting
  • Int'l Joint Research