title: Activation of receptor for advanced glycation end products contributes to aortic remodeling and endothelial dysfunction in sinoaortic denervated rats.
abstract: 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.
  
  
  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 μg 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 NFκB 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, 98th Military Hospital, 9 CheZhan Road, Huzhou 313000, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Jin-Zhong
authors.initials: JZ
authors.lastname: Feng
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qiu
authors.forename: Feng-Bin
authors.initials: FB
authors.lastname: Yu
authors.forename: Jian-Zhong
authors.initials: JZ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Feng
authors.initials: F
authors.lastname: Yu
authors.forename: Guo-Kun
authors.initials: GK
authors.lastname: Wang
authors.forename: Li-Na
authors.initials: LN
authors.lastname: An
authors.forename: Fei-Hua
authors.initials: FH
authors.lastname: Ni
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Xian-Xian
authors.initials: XX
authors.lastname: Zhao
authors.forename: Yong-Wen
authors.initials: YW
authors.lastname: Qin
authors.forename: He-De
authors.initials: HD
authors.lastname: Luo
mesh_terms: D000449:Aldehyde Reductase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D017763:Autonomic Denervation; D017704:Baroreflex / Q000502:physiology; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000294:innervation / Q000378:metabolism* / Q000503:physiopathology; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D014657:Vasculitis / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009569:Nitric Oxide; D000449:Aldehyde Reductase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007791:Lactoylglutathione Lyase
keywords: Aortic remodeling; Endothelial dysfunction; Inflammation; Nitric oxide; Oxidative stress; Receptor for advanced glycation end products; Sinoaortic denervation