Minireview Advanced glycation and endothelial functions: A link towards vascular complications in diabetes Armando Rojas a , Miguel A. Morales b, * a Facultad de Medicina, Universidad de Chile, Santiago de Chile, Chile b Laboratorio de Farmacodinamia y Fitofarmacologı ´a, Instituto de Ciencias Biome ´dicas (ICBM), Programa de Farmacologı ´a Molecular y Clı ´nica, Facultad de Medicina, Universidad de Chile, Avda. Independencia #1027, Santiago de Chile, Chile Received 24 March 2004; accepted 14 July 2004 Abstract The formation of advanced glycation end-products (AGEs), also called the Maillard reaction, occurs ubiquitously and irreversibly in patients with diabetes mellitus, and its consequences are especially relevant to vascular dysfunctions. The interaction of AGEs with their receptors (RAGE) has been implicated in the development of vascular complications. This interaction elicits remarkable vascular cell changes analogous to those observed in diabetes mellitus, including angiogenic and thrombogenic responses of endothelial cells, increased oxidative stress, and functional alterations in vascular tone control. This review focuses on AGEs formation, the interaction with their specific receptors and how the triggered intracellular events determine functional alterations of vascular endothelium. Finally, some potential pharmacological approaches undertaken to circumvent the deleterious effects of AGEs are also discussed. D 2004 Elsevier Inc. All rights reserved. Keywords: Advanced glycation; Diabetes; Endothelium; Vascular complications Contents Introduction ....................................................... 716 Advanced glycation .............................................. 717 Interacting with endothelium. AGE receptors ................................. 718 0024-3205/$ - see front matter D 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.lfs.2004.09.011 * Corresponding author. Tel.: +56 2 678 6711; fax: +56 2 737 2783. E-mail address: mmorales@med.uchile.cl (M.A. Morales). Life Sciences 76 (2004) 715 – 730 www.elsevier.com/locate/lifescie