Role of advanced glycation end products in cardiovascular disease

Figure 4 Intracellular effects of AGEs after AGE/RAGE binding. Diagrammatic representation of AGE/RAGE interaction on the surface of an endothelial cell leads to transduction of a signalling cascade; activates nicotinamide adenine dinucleotide phosphate oxidase and enhances ROS production and phosphorylate p21 RAS and MAPKs. Moreover, the AGE/RAGE interaction induces signalling through activation of p38 MAPK. A main step in AGE/RAGE signalling is activation of NF-κB and its translocation to the nucleus, where it enhances transcription of target genes as endothelin-1, ICAM-1, E-selectin and tissue factor. Hence, AGE/RAGE binding triggers an inflammatory cascade. AGE may decrease NO availability by reducing eNOS activity and by inactivating NO. AGE: Advanced glycation end-product; RAGE: Receptor for advanced glycation end products; ROS: Reactive oxygen species; MAPKs: Mitogen-activated protein kinases; ERK1/2: Extracellular signal-regulated kinase 1/2; NF-κB: Nuclear factor kappa B; ICAM-1: Intercellular adhesion molecule-1; VCAM-1: Vascular cell adhesion molecule-1; VEGF: Vascular endothelial growth factor; IL-1α: Interleukin-1α; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; eNOS: Endothelial nitric oxide synthase; NO: Nitric oxide.