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Influence of non-vascular cells in accelerated coronary aging in diabetes

Research Project

Project/Area Number 19F19708
Research Category

Grant-in-Aid for JSPS Fellows

Allocation TypeSingle-year Grants
Section外国
Review Section Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Pearson James  国立研究開発法人国立循環器病研究センター, 研究所, 部長 (30261390)

Co-Investigator(Kenkyū-buntansha) NGO JENNIFER  国立研究開発法人国立循環器病研究センター, 研究所, 外国人特別研究員
Project Period (FY) 2019-07-24 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2020: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2019: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordscoronary vessels / diabetes / ageing / oxidative stress / vasodilators / aging
Outline of Research at the Start

To determine whether vascular aging in diabetes is caused by early inflammation and oxidative stress that develops in heart muscle cells and immune cells. In addition, we aim to identify whether vascular aging is then exacerbated by aging of cells lining our blood vessels due to inactivity.

Outline of Annual Research Achievements

Metabolome analyses of myocardium from senescence accelerated mice (SAMP8) and resistance mice (SAMR1) on a high fat diet (HFD) revealed that in SAMP8 mice glycolysis was inhibited and abnormal purine metabolism increased xanthine oxidase (XO) activation and ROS generation relative to SAMR1 mice. While antioxidant GSH was upregulated and L-arginine availability was maintained in the HFD SAMP8 mouse hearts we found that eNOS phosphorylation at Ser1177 was downregulated in SAMP8 and upregulated in SAMR1 on the HFD. Notably, this resulted in reduced coronary microvessel perfusion (microangiography), but not macrovessels in the HFD SAMP8 mice. Importantly, high intensity exercise training for 8wks restored microvessel perfusion in the HFD SAMP8 through an increased NO contribution.

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (3 results)

All 2021 2019

All Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] β-blockade prevents coronary macro- and microvascular dysfunction induced by a high salt diet and insulin resistance in the Goto?Kakizaki rat2021

    • Author(s)
      Pearson James T. et al
    • Journal Title

      Clinical Science

      Volume: 135 Issue: 2 Pages: 327-346

    • DOI

      10.1042/cs20201441

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Ghrelin and vascular protection.2019

    • Author(s)
      Pearson JT, Shirai M, Sukumaran V, Du CK, Tsuchimochi H, Sonobe T, Waddingham MT, Katare R, Schwenke DO.
    • Journal Title

      Vascular Biology

      Volume: 1 Issue: 1 Pages: H97-H102

    • DOI

      10.1530/vb-19-0024

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Coronary nitric oxide bioavailability is reduced by xanthine oxidase and nitrosative stress on a high fat diet but restored by high intensity exercise in senescence-accelerated mice2021

    • Author(s)
      James Pearson
    • Organizer
      第98回日本生理学会大会
    • Related Report
      2020 Annual Research Report

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Published: 2019-07-30   Modified: 2024-03-26  

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