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Pathological role of receptor for advanced glycation end products in calcified aortic valve stenosis

Research Project

Project/Area Number 17K16601
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular surgery
Research InstitutionKurume University

Principal Investigator

Saku Kosuke  久留米大学, 医学部, 助教 (50771862)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords大動脈弁狭窄症 / AGEs / RAGE / 慢性炎症 / 動脈硬化 / AGEs / 平滑筋細胞 / 外科
Outline of Final Research Achievements

Aortic stenosis (AS) is highly prevalent in patients with atherosclerotic cardiovascular disease. Advanced glycation end products (AGEs) and the receptor for AGEs (RAGE) play a pivotal role for vascular calcification in atherosclerosis. We hypothesize that AGEs-RAGE axis could also be involved in the pathophysiological mechanism of AS.
54 patients with AS who underwent aortic valve replacement (AVR) were enrolled from 2014 to 2016. 16 deceased specimens and 70 serum samples without heart disease was used as controls. Valvular RAGE expression in AS was higher than controls. RAGE and αSMA were co-expressed, which were partially co-stained with osteocalcin and ALP. Serum levels of RAGE were higher in AS than controls. RAGE was independently correlated with changes in left ventricular function after AVR .In conclusions, our results suggests that RAGE may play a role in the pathogenesis of calcified AS, being a prognostic marker of patients with AS after AVR.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、大動脈弁狭窄症(AS)は動脈硬化と類似した病態を有し、終末糖化産物(AGEs)とその受容体RAGE(Receptor for AGEs)が、ASの病態の進行に関与することが示唆された。また、血清RAGEは、大動脈弁置換術後の心機能と相関していることも示された。以上から、RAGEはASに対する内科的治療のターゲット及び治療効果判定になる得る可能性があるだけでなく、ASに対する大動脈弁置換術後の予後を表すバイオマーカーにもなり得る可能性が考えられた。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (3 results)

All 2020 2018

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] Pathological role of receptor for advanced glycation end products in calcified aortic valve stenosis2020

    • Author(s)
      Kosuke Saku
    • Journal Title

      Journal of the American Heart Association

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Role of RAGE in aortic valve stenosis2018

    • Author(s)
      朔 浩介
    • Organizer
      日本循環器学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of RAGE in aortic valve stenosis2018

    • Author(s)
      Kosuke Saku
    • Organizer
      Heart Valve Society
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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