Activation of receptor for advanced glycation end products contributes to aortic remodeling and endothelial dysfunction in sinoaortic denervated rats

作者：Wu Feng; Feng Jin Zhong; Qiu Yi Hua; Yu Feng Bin; Zhang Jian Zhong; Zhou Wei; Yu Feng; Wang Guo Kun; An Li Na; Ni Fei Hua; Wu Hong; Zhao Xian Xian; Qin Yong Wen; Luo He De^*

来源：Atherosclerosis, 2013, 229(2): 287-294.

DOI：10.1016/j.atherosclerosis.2013.04.033

• Sinoaortic denervation
• Receptor for advanced glycation end products
• Aortic remodeling
• Endothelial dysfunction
• Oxidative stress
• Inflammation
• Nitric oxide

Objective: The aim of present study was to test the hypothesis that activation of receptor for advanced glycation end products (RAGE) pathway contributes to aortic remodeling and endothelial dysfunction in sinoaortic denervated (SAD) rats. %26lt;br%26gt;Methods and results: Experiment 1: 8 weeks after sinoaortic denervation, aortas were removed for measurement of AGE/RAGE pathway. Sinoaortic denervation in rats resulted in enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE in aortas. Experiment 2: 5 weeks after sinoaortic denervation, the rats received intraperitoneal injections of 500 mu g soluble RAGE (sRAGE) daily for 3 weeks. Treatment of SAD rats with sRAGE attenuated aortic remodeling, marked by reduction in AW/length, wall thickness, proliferation of SMC, and collagen deposition, and improvement of endothelial function. Treatment of SAD rats with sRAGE abated aortic oxidative stress, marked by reduction in formation of malondialdehyde, reactive oxygen species, superoxide, peroxynitrite and 3-nitrotyrosine, and enhancement of ratio of GSH/GSSG. Treatment of SAD rats with sRAGE attenuated aortic mitochondrial dysfunction. Treatment of SAD rats with sRAGE suppressed aortic NFkB nuclear translocation and inflammation. Treatment of SAD rats with sRAGE restored aortic NO formation through upregulating eNOS and dimethylarginine dimethylaminohydrolase-2 and downregulating protein arginine methyltransferase-1. %26lt;br%26gt;Conclusion: Activated RAGE contributed to aortic remodeling and endothelial dysfunction in SAD rats, possibly via induction of oxidative stress and inflammation, impairment of mitochondrial function, and reduction in NO bioavailability.

• 出版日期2013-8
• 单位中国人民解放军第二军医大学