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Elucidation of molecular mechanism of systemic vascular changes due to aortic stenosis-role of platelet activation by shear stress

Research Project

Project/Area Number 20K09130
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionKagoshima University

Principal Investigator

Kanda Hideaki  鹿児島大学, 医歯学域医学系, 助教 (50598274)

Co-Investigator(Kenkyū-buntansha) 松本 和久  鹿児島大学, 医歯学域鹿児島大学病院, 助教 (10363631)
山口 宗一  鹿児島大学, 医歯学域医学系, 准教授 (20325814)
井本 浩  鹿児島大学, 医歯学域医学系, 教授 (60274461)
橋口 照人  鹿児島大学, 医歯学域医学系, 教授 (70250917)
大川 政士  鹿児島大学, 鹿児島大学病院, 医員 (90869322)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords大動脈弁狭窄症 / ずり応力 / 血小板 / 血管内皮増殖因子 / VEGF / マイクロRNA
Outline of Research at the Start

ASでは、狭窄弁による乱流から生じるシアストレスがVon Willebland因子活性に影響を与えている。また血小板は、VEGFやセロトニン、マイクロRNA (miRNA)を内在しており、シアストレスで活性化した血小板は内在因子やその機能も変化する。ASでも狭窄弁によるシアストレスが血小板機能を変化し、心不全や大動脈弁、移植人工弁に影響している可能性がある。本研究は経時的に採取した血液検体より分離した血小板を用い、巨核球系培養細胞を用いた基礎研究と合わせて、ASでのシアストレスが活性化した血小板miRNA、血小板内在因子が病態に与える影響を解明、予防可能な創薬に繋がると考えている。

Outline of Final Research Achievements

Long-term blood samples from patients with aortic stenosis (AS) were analyzed for platelet-related factors. Vascular endothelial growth factor (VEGF), which is abundant in platelets, was higher in AS patients than before surgery. Among them, VEGF-165, which is a subtype that is particularly abundant in platelets, was higher than before surgery even in the first year. It was suggested that although blood flow improves with aortic valve replacement, the prothetic valve may affect platelets. Since the number of subjects was small and the VEGF of the platelets themselves could not be measured, it was not possible to make a firm statement, it was considered necessary to accumulate cases and further analysis in the future.

Academic Significance and Societal Importance of the Research Achievements

大動脈弁狭窄症および大動脈弁置換術で使用する人工弁が血小板に影響を与えVEGFの推移を起こしている可能性が示唆された。また、大動脈弁狭窄症患者では術前からVEGFの血中濃度が高いことが考えられ、病態の進行に影響を及ぼしている可能性がある。さらには、弁置換術を行った後もVEGF血中濃度が高く、術後患者の状態や移植した人工弁に影響を与えている
可能性が考えられた。まだ検討が十分ではないが、本研究と同様に循環器系の他疾患を検討していくことも可能と考えられた。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (2 results)

All 2021

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Dynamic changes in platelets caused by shear stress in aortic valve stenosis2021

    • Author(s)
      Hideaki Kanda, Munekazu Yamakuchi, Kazuhisa Matsumoto, Kosuke Mukaihara, Yoshiya Shigehisa, Shuji Tachioka, Masashi Okawa, Kazunori Takenouchi, Yoko Oyama, Teruto Hashiguchi, and Yutaka Imotoa
    • Journal Title

      Clinical Hemorheology and Microcirculation

      Volume: 77 Issue: 1 Pages: 71-81

    • DOI

      10.3233/ch-200928

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The significance of platelet dynamics in perioperative period of aortic valve replacement for aortic valve stenosis2021

    • Author(s)
      Hideaki KANDA, Munekazu YAMAKUCHI, Kazuhisa MATSUMOTO, Kosuke MUKAIHARA, Yoshiya SHIGEHISA, Shuji TACHIOKA, Masashi OKAWA, Kazunori TAKENOUCHI, Yoko OYAMA, Teruto HASHIGUCHI, Yutaka IMOTO
    • Organizer
      The Asian-Pacific Society on Thrombosis and Hemostasis
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research

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Published: 2020-04-28   Modified: 2024-01-30  

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