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 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. Copyright (c) 2009. Published by Elsevier Ireland Ltd.
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 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. Copyright (c) 2009. Published by Elsevier Ireland Ltd.
Authors: Douglas Ganini; Marcelo Christoff; Marilyn Ehrenshaft; Maria B Kadiiska; Ronald P Mason; Etelvino J H Bechara Journal: Free Radic Biol Med Date: 2011-05-08 Impact factor: 7.376
Authors: Sowmya Soman; Rajesh Raju; Varot K Sandhya; Jayshree Advani; Aafaque Ahmad Khan; H C Harsha; T S Keshava Prasad; P R Sudhakaran; Akhilesh Pandey; Puneeth K Adishesha Journal: J Cell Commun Signal Date: 2012-11-19 Impact factor: 5.782