Atherosclerosis and restenosis: is there a role for RAGE?

Diabetic vascular complications are a major cause of morbidity and mortality. Furthermore, such vascular disease is only incompletely explained by "traditional" risk factors in the nondiabetic complications. This situation has prompted the search for factors contributing to the pathogenesis of accelerated and more severe vascular disease in patients with diabetes. We review evidence that receptor for advanced glycation end products (RAGE), via its interaction with ligands, serves as a cofactor exacerbating diabetic vascular disease. RAGE is a member of the immunoglobulin superfamily of cell surface molecules with a diverse repertoire of ligands reminiscent of pattern recognition receptors. In the diabetic milieu, two classes of RAGE ligands, products of nonenzymatic glycoxidation and S100 proteins, appear to drive receptor-mediated cellular activation and, potentially, acceleration of vascular disease.