The receptor for advanced glycation endproducts (RAGE) and cardiovascular disease.
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.
Yan
Shi Fang
SF
Division of Surgical Science, Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Ramasamy
Ravichandran
R
Schmidt
Ann Marie
AM
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
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic