The role of RAGE, MAPK and NF-κB pathway in the advanced glycation end-products induced HUVECs dysfunction

Abstract

OBJECTIVE: The objective of this study was to investigate how receptor for advanced glycation end-products–mitogen-activated protein kinase–nuclear factor-kappa B (MAPK-NF-κB) pathway is involved in advanced glycation end-product (AGE)-induced human umbilical venous endothelial cell (HUVEC) dysfunction. MATERIALS AND METHODS: HUVECs were cultured with AGEs, anti-RAGE, inhibitors of MAPK or NF-κB respectively. Then we detected endothelial nitric oxide synthase (eNOS) activation, nitric oxide (NO) concentration, cell migration ability, and RAGE expression of HUVECs. RESULTS: AGEs depressed eNOS activation, decreased NO concentration, impaired endothelial cell (EC) migration, and upregulated RAGE expression, which could be recovered by p38 inhibitor and extracellular regulated protein kinases (ERK) inhibitor. However, these effects could not be recovered by NF-κB inhibitor. CONCLUSIONS: AGEs increase RAGE expression and decrease NO release and migration of HUVECs through RAGE-MAPK pathway, but not NF-κB pathway.

Keywords

• advanced glycation end-products
• endothelial dysfunction
• mitogen-activated protein kinase
• nuclear factor-kappa b