title: AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB pathways.
abstract: OBJECTIVE
  Advanced glycation end products (AGEs) and vascular adventitial fibroblasts (AFs) are involved in diabetes-related vascular complications. However, the effect of AGEs on AFs remains unclear. The aim of this study was to observe the impact of AGEs on cell migration capacity and associated inflammatory responses of AFs.
  
  
  RESULTS
  Isolated vascular AFs of Sprague-Dawley rats were cultured, harvested after 24h synchronization and challenged with AGE-HSA. AGE-HSA upregulated the expression of receptor for advanced glycation end products (RAGE), significantly increased the migration capacity and inflammatory mediators MCP-1, IL-6, VCAM-1 expressions on AFs. These effects could be significantly attenuated by anti-RAGE neutralizing antibody, p38, ERK1/2 and JNK MAPK inhibitors as well as by candesartan. AGE-HAS also upregulated NF-kappaB transcriptional activity and I-kappaB-alpha phosphorylation, effect that was significantly inhibited by candesartan.
  
  
  CONCLUSIONS
  AGE-HSA increased the migration capacity and inflammatory responses of rat AFs via RAGE-MAPK-NF-kappaB pathways. Candesartan effectively inhibited these effects which might be a novel vascular protection mechanism of candesartan.
authors: Department of Cardiology, Second Hospital Affiliated to the Second Military Medical University, 415 Fengyang Road, Shanghai, People's Republic of China.
authors: YaYang
authors: Y
authors: Liu
authors: Chun
authors: C
authors: Liang
authors: Xing
authors: X
authors: Liu
authors: Bin
authors: B
authors: Liao
authors: Xiaoming
authors: X
authors: Pan
authors: Yusheng
authors: Y
authors: Ren
authors: Min
authors: M
authors: Fan
authors: Mei
authors: M
authors: Li
authors: Zhiqing
authors: Z
authors: He
authors: Jianxiang
authors: J
authors: Wu
authors: ZongGui
authors: Z
authors: Wu
mesh_terms: D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D005347:Fibroblasts / Q000276:immunology*; D017127:Glycation End Products, Advanced / Q000502:physiology*; D007249:Inflammation / Q000276:immunology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D020928:Mitogen-Activated Protein Kinases