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

对衰老加速小鼠(SAMP8)和抵抗小鼠(SAMR1)高脂饮食心肌的代谢组学分析表明，SAMP8小鼠糖酵解受到抑制，嘌呤代谢异常增加了黄嘌呤氧化酶(XO)的活性和ROS的产生。在HFDSAMP8小鼠心脏中，抗氧化剂GSH表达上调，L精氨酸利用率保持不变。我们发现，在HFDSAMP8中，Ser1177位eNOS的磷酸化水平在SAMP8中下调，在SAMR1中上调。值得注意的是，这导致HFD SAMP8小鼠的冠状动脉微血管灌注量(微血管造影术)减少，但大血管没有减少。重要的是，8周的大强度运动训练通过增加NO的贡献恢复了HFD SAMP8的微血管灌流。

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.