title: The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease.
abstract: Recent and compelling investigation has expanded our view of the biological settings in which the products of nonenzymatic glycation and oxidation of proteins and lipids - the advanced glycation endproducts (AGEs) - form and accumulate. Beyond diabetes, natural ageing and renal failure, AGEs form in inflammation, oxidative stress and in ischaemia-reperfusion. The chief signal transduction receptor for AGEs - the receptor for AGEs (RAGE) - is a multiligand-binding member of the immunoglobulin superfamily. In addition to AGEs, RAGE binds certain members of the S100/calgranulin family, high-mobility group box 1 (HMGB1), and beta-amyloid peptide and beta-sheet fibrils. Recent studies demonstrate beneficial effects of RAGE antagonism and genetic deletion in rodent models of atherosclerosis and ischaemia-reperfusion injury in the heart and great vessels. Experimental evidence is accruing that RAGE ligand generation and release during ischaemia-reperfusion may signal through RAGE, thus suggesting that antagonism of this receptor might provide a novel form of therapeutic intervention in heart disease. However, it is plausible that innate, tissue-regenerative roles for these RAGE ligands may also impact the failing heart - perhaps through RAGE and/or distinct receptors. In this review, we focus on RAGE and the consequences of its activation in the cardiovasculature.
authors.affiliation: Division of Surgical Science, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Shi Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000473:pathology*; D006801:Humans; D007249:Inflammation; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D012038:Regeneration; D015427:Reperfusion Injury; D015398:Signal Transduction
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic