AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappa B pathways

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. Methods and results: Isolated vascular AFs of Sprague-Dawley rats were cultured, harvested after 24 h 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-kappa B transcriptional activity and I-kappa B-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-kappa B pathways. Candesartan effectively inhibited these effects which might be a novel vascular protection mechanism of candesartan. (C) 2009 Published by Elsevier Ireland Ltd.