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2020 Fiscal Year Annual Research Report

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

Research Project

Project/Area Number 19F19708
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
Keywordscoronary vessels / diabetes / ageing / oxidative stress / vasodilators
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。

  • Research Products

    (2 results)

All 2021

All Journal Article (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.、Thambyah Hamish P.、Waddingham Mark T.、Inagaki Tadakatsu、Sukumaran Vijayakumar、Ngo Jennifer P.、Ow Connie P.C.、Sonobe Takashi、Chen Yi Ching、Edgley Amanda J.、Fujii Yutaka、Du Cheng-Kun、Zhan Dong-Yun、Umetani Keiji、Kelly Darren J.、Tsuchimochi Hirotsugu、Shirai Mikiyasu
    • Journal Title

      Clinical Science

      Volume: 135 Pages: 327~346

    • DOI

      10.1042/CS20201441

  • [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

URL: 

Published: 2021-12-27  

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