The research on regulation of vascular remodeling by CD271-positive cells

• Project/Area Number: 18K08031
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kanazawa University
• Principal Investigator: Takashima Shinichiro 金沢大学, 附属病院, 助教 (60547165)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 末梢血白血球 / 骨髄由来細胞 / 急性冠症候群 / 血管リモデリング / バイオマーカー / NGFR / 動脈硬化 / 末梢血幹細胞 / 間葉系幹細胞

Outline of Final Research Achievements

1. Basic research: Carotid ligation-induced intimal thickening increased in the CD271-gene deficiency model. Apoptosis in the neointima formed in the CD271 gene deficiency model was reduced. Moreover, CD271-positive cells were suggested to be derived from bone marrow.
2. Clinical study: Peripheral blood CD271-positive cell count increased 1.5-fold on day 3 of an acute coronary syndrome (ACS) compared to day 0 of onset. The rate of change in plaque volume at 9 months was inversely correlated with the number of CD271-positive cells on day 0 of ACS onset. Multivariate analysis showed that the number of CD271 positive cells on day 0 of ACS onset was a negative predictor of the plaque volume change rate of the non-targeted lesion at the 9 months.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、骨髄由来の末梢血白血球中のCD271が動脈硬化の病態生理に関与する可能性が示された。また急性冠症候群患者の冠動脈予後を発症時に予測する新規バイオマーカーとなる可能性が示された。将来的には新しい抗動脈硬化治療(CD271陽性細胞動員・補充治療など)の研究開発への波及効果が期待される。

Research Products

• [Presentation] Bone marrow-derived NGFR+ cells regulate arterial remodeling and those poor mobilizations in peripheral blood in acute coronary syndrome predicts plaque progression at the non-targeted lesion (2020)
  • Author(s): Takashima S, Usui S, Matsuura S, Goten C, Inoue O, Ohtani K, Kubota K, Sakata K, Kawashiri M, Takamura M
  • Organizer: ESC Congress 2020
  • Int'l Joint Research
• [Presentation] Low level of circulating CD271-positive mononuclear cells in acute coronary syndrome predicts plaque progression at de novo lesion (2020)
  • Author(s): Takashima S, Usui S, Matsuura S, Inoue O, Goten C, Hamaoka T, Kato T, Murai H, Furusho H, Ohtani K, Kubota K, Sakata K, Kawashiri M, Takamura M
  • Organizer: JCS2020 Annual Meeting
• [Presentation] Low Level of Circulating CD271-positive Mononuclear Cells in Acute Coronary Syndrome Predicts Plaque Progression at de Novo Lesion (2019)
  • Author(s): Shinichiro Takashima
  • Organizer: 日本循環器学会学術集会
• [Presentation] Mobilization of Circulating CD271-positive Mononuclear Cells in Acute Coronary Syndrome Reflects the Characteristics of Coronary Atheroma (2018)
  • Author(s): Shintaro Matsuura, Shinichiro Takashima
  • Organizer: AHA Scientific Session 2018
  • Int'l Joint Research