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 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
Host Researcher	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)
Foreign Research Fellow	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)
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。