Animal Models and Novel Insights Into the Vascular Complications of Diabetes

Abstract—Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Engagement of RAGE by its signal transduction ligands evokes inflammatory cell infiltration and activation in the vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and superimposed stresses such as hyperlipidemia or acute balloon/endothelial denuding arterial injury, the ligand–RAGE axis amplifies vascular stress and accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we review the use of rodent models to test these concepts. Taken together, our findings support the premise that RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. Future studies must rigorously test the potential impact of RAGE blockade in human subjects; such trials are on the horizon. (Arterioscler Thromb Vasc Biol. 2004;24:1342-1349.) Key Words: diabetes animal models receptors inflammation signal transduction The receptor for advanced glycation end products (RAGE)is a multi-ligand member of the immunoglobulin super-family of cell surface molecules.1,2 Its ability to recognize multiple classes of ligands, such as advanced glycation end products (AGEs), S100/calgranulins, amphoterin, amyloid- peptide and -sheet fibrils, and MAC-1,3–8 suggests that the repertoire of RAGE-dependent effects in the tissues may b