Advanced glycation end products depress function of endothelial progenitor cells via p38 and ERK 1/2 mitogen-activated protein kinase pathways

作者：Sun, Chengbo; Liang, Chun; Ren, Yusheng; Zhen, Yi; He, Zhiqing; Wang, Hua; Tan, Hongbing; Pan, Xiaoming; Wu, Zonggui^*

来源：Basic Research in Cardiology, 2009, 104(1): 42-49.

DOI：10.1007/s00395-008-0738-8

• endothelial progenitor cells
• advanced glycation end products
• receptor for advanced glycation end products
• apoptosis
• migration

Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play divergent roles in the process of atherosclerosis. We investigated the effects of AGE-human serum albumin (AGE-HSA) on receptor expression for AGEs (RAGE) and EPCs apoptosis.
The human mononuclear cells were obtained by Ficoll density gradient centrifugation and cultured in M199 medium containing rh-VEGF (30 ng/ml), rh-b-FGF(6 ng/ml) and 20% NBCS for 8 days. The adhesive EPCs were sequentially harvested after 24 h synchronization and challenged with AGE-HSA (concentration range from 0 to 300 A mu g/ml) for 24 h and 200 A mu g/ml AGE-HSA (time range from 0 to 36 h). EPCs apoptosis and migration were determined, expressions of RAGE, phosphorylated ERK1/2, JNK and p38 mitogen-activated protein kinase (MAPK) of EPCs were quantified by fluorescent quantitation RT-PCR and Western-blot, effect of AGE-HSA on NF-kappa B activtiy was determined by EMSA (electrophoretic mobility shift assay) in the presence and absence of special MAPK pathways pathway inhibitors.
AGE-HSA upregulated the expression of RAGE, this effect could be significantly inhibited by p38 MAPK and ERK MAPK inhibitor, but not by JNK MAPK inhibitor. AGE-HSA also promoted EPCs apoptosis and inhibited EPCs migration and increased NF-kappa B activity, these effects could be significantly attenuated by the anti-RAGE neutralizing antibody as well as by p38 and ERK MAPK inhibitors.
AGE-HSA could promote atherosclerosis by upregulating EPCs RAGE expressions and promoting EPCs apoptosis via p38, ERK MAPK pathways, activation of NF-kappa B might also play a role in this process.

• 出版日期2009-1
• 单位天津市中医药研究院附属医院; 中国人民解放军第二军医大学