Receptor for advanced glycation endproducts and atherosclerosis: From basic mechanisms to clinical implications.
The receptor for advanced glycation endproducts (RAGE) is a member of the immunoglobulin superfamily of cell-surface molecules with a diverse repertoire of ligands. In the atherosclerotic milieu, three classes of RAGE ligands, i.e., products of non-enzymatic glycoxidation, S100 proteins and amphoterin, appear to drive receptor-mediated cellular activation and potentially, acceleration of vascular disease. The interaction of RAGE-ligands effectively modulates several steps of atherogenesis, triggering an inflammatory-proliferative process and furthermore, critically contributing to propagation of vascular perturbation, mainly in diabetes. RAGE has a circulating truncated variant isoform, soluble RAGE (sRAGE), corresponding to its extracellular domain only. By competing with cell-surface RAGE for ligand binding, sRAGE may contribute to the removal/neutralization of circulating ligands thus functioning as a decoy. The critical role of RAGE in the chronic vascular inflammation processes highlights this receptor-ligand axis as a possible and attractive candidate for therapeutic intervention to limit vascular damage and its associated clinical disorders.
Basta
Giuseppina
G
CNR, Institute of Clinical Physiology, San Cataldo Research Area, Via Moruzzi 1, 56124 Pisa, Italy. Electronic address: lapina@ifc.cnr.it.
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000503:physiopathology*; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000502:physiology; D024243:HMGB1 Protein; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology*; D009418:S100 Proteins / Q000502:physiology