AGEs increased migration and inflammatory responses of adventitial fibroblasts via RAGE, MAPK and NF-kappaB 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.


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.
Liu
YaYang
Y
Department of Cardiology, Second Hospital Affiliated to the Second Military Medical University, 415 Fengyang Road, Shanghai, People's Republic of China.
Liang
Chun
C
Liu
Xing
X
Liao
Bin
B
Pan
Xiaoming
X
Ren
Yusheng
Y
Fan
Min
M
Li
Mei
M
He
Zhiqing
Z
Wu
Jianxiang
J
Wu
ZongGui
Z
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
D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D020928:Mitogen-Activated Protein Kinases