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

非血管细胞对糖尿病冠脉加速老化的影响

• 批准号: 19F19708
• 负责人: Pearson James
• 金额: $ 1.47万
• 依托单位: National Cardiovascular Center Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-07-24 至 2021-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19F19708/
• 关键词: coronary vessels; diabetes; ageing; oxidative stress; vasodilators; aging

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.

对高脂饮食（HFD）加速衰老小鼠（SAMP 8）和抵抗小鼠（SAMR 1）心肌的代谢组学分析显示，相对于SAMR 1小鼠，SAMP 8小鼠糖酵解被抑制，嘌呤代谢异常增加黄嘌呤氧化酶（XO）活化和ROS产生。在HFD SAMP 8小鼠心脏中，虽然抗氧化剂GSH被上调，L-精氨酸的可用性得以维持，但我们发现，在HFD上，SAMP 8中Ser 1177处的eNOS磷酸化被下调，而在SAMR 1中被上调。值得注意的是，这导致HFD SAMP 8小鼠中冠状动脉微血管灌注（微血管造影）减少，但大血管没有减少。重要的是，8周的高强度运动训练通过增加NO贡献来恢复HFD SAMP 8的微血管灌注。

项目成果

β-blockade prevents coronary macro- and microvascular dysfunction induced by a high salt diet and insulin resistance in the Goto?Kakizaki rat

β-阻断可预防 Goto?Kakizaki 大鼠由高盐饮食和胰岛素抵抗引起的冠状动脉大血管和微血管功能障碍

• DOI: 10.1042/cs20201441
• 发表时间: 2021
• 期刊: Clinical Science
• 影响因子: 6
• 作者: Pearson James T. et al

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

黄嘌呤氧化酶和高脂肪饮食的亚硝化应激会降低冠状动脉一氧化氮的生物利用度，但在加速衰老的小鼠中，高强度运动可以恢复冠状动脉一氧化氮的生物利用度

• 发表时间: 2021
• 作者: Pearson JT;Shirai M;Sukumaran V;Du CK;Tsuchimochi H;Sonobe T;Waddingham MT;Katare R;Schwenke DO.;James Pearson
• 通讯作者: James Pearson

Ghrelin and vascular protection.

• DOI: 10.1530/vb-19-0024
• 发表时间: 2019-01-01
• 期刊: Vascular biology (Bristol, England)
• 作者: Pearson, James T;Shirai, Mikiyasu;Schwenke, Daryl O
• 通讯作者: Schwenke, Daryl O