Department of Cardiology, Second Hospital Affiliated to the Second Military Medical University, 415 Fengyang Road, Shanghai, People's Republic of China.
Atherosclerosis. 2010 Jan;208(1):34-42. doi: 10.1016/j.atherosclerosis.2009.06.007. Epub 2009 Jun 17.
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.
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.
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.
糖基化终产物（AGEs）和血管外膜成纤维细胞（AFs）参与糖尿病相关的血管并发症。然而，AGEs 对 AFs 的影响尚不清楚。本研究旨在观察 AGEs 对 AFs 细胞迁移能力及相关炎症反应的影响。
培养 Sprague-Dawley 大鼠血管 AFs，同步培养 24 小时后收获，用 AGE-HSA 进行刺激。AGE-HSA 上调晚期糖基化终产物受体（RAGE）的表达，显著增加 AFs 的迁移能力和炎症介质 MCP-1、IL-6、VCAM-1 的表达。抗 RAGE 中和抗体、p38、ERK1/2 和 JNK MAPK 抑制剂以及坎地沙坦均可显著减弱这些作用。AGE-HAS 还上调了 NF-κB 转录活性和 I-κB-α磷酸化，坎地沙坦可显著抑制这些作用。
AGE-HSA 通过 RAGE-MAPK-NF-κB 途径增加大鼠 AFs 的迁移能力和炎症反应。坎地沙坦能有效抑制这些作用，这可能是坎地沙坦的一种新型血管保护机制。
