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

• Project/Area Number: 19F19708
• Research Category: Grant-in-Aid for JSPS Fellows
• Allocation Type: Single-year Grants
• Section: 外国
• Review Section: Basic Section 44050:Animal physiological chemistry, physiology and behavioral biology-related
• Research Institution: National 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: ¥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)
• Keywords: coronary 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。

Research Products

• [Journal Article] β-blockade prevents coronary macro- and microvascular dysfunction induced by a high salt diet and insulin resistance in the Goto?Kakizaki rat (2021)
  • Author(s): Pearson James T. et al
  • Journal Title: Clinical Science Volume: 135 Issue: 2 Pages: 327-346
  • DOI: 10.1042/cs20201441
  • 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
  • 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 mice (2021)
  • Author(s): James Pearson
  • Organizer: 第９８回日本生理学会大会