title: RAGE and its ligands: a lasting memory in diabetic complications?
abstract: The complications of diabetes are myriad and represent a rising cause of morbidity and mortality, particularly in the Western world. The update of the Diabetes Control and Clinical Trials Group/Epidemiology of Diabetes Interventions and Complications Research Group (DCCT/EDIC) suggested that previous strict control of hyperglycaemia was associated with reduced carotid atherosclerosis compared to conventional treatment, even after levels of glycosylated haemoglobin between the two treatment groups became indistinguishable. These intriguing findings prompt the key question, why does the blood vessel 'remember'? This review focuses on the hypothesis that the ligand/RAGE axis contributes importantly to glycaemic 'memory'. Studies in rodent models of diabetes suggest that blockade or genetic modification of RAGE suppress diabetes-associated progression of atherosclerosis, exaggerated neointimal expansion consequent to acute arterial injury, and cardiac dysfunction. We propose that therapeutic RAGE blockade will intercept maladaptive diabetes-associated memory in the vessel wall and provide cardiovascular protection in diabetes.
authors.affiliation: Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
authors.forename: Shi-Fang
authors.initials: SF
authors.lastname: Yan
authors.forename: Ravichandran
authors.initials: R
authors.lastname: Ramasamy
authors.forename: Loredana G
authors.initials: LG
authors.lastname: Bucciarelli
authors.forename: Thoralf
authors.initials: T
authors.lastname: Wendt
authors.forename: Larisse K
authors.initials: LK
authors.lastname: Lee
authors.forename: Barry I
authors.initials: BI
authors.lastname: Hudson
authors.forename: David M
authors.initials: DM
authors.lastname: Stern
authors.forename: Evanthia
authors.initials: E
authors.lastname: Lalla
authors.forename: Shi
authors.initials: S
authors.lastname: DU Yan
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Rong
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Naka
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism / Q000473:pathology; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D018821:CD18 Antigens / Q000378:metabolism; D048909:Diabetes Complications / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D039841:Leukocyte L1 Antigen Complex / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D009206:Myocardium / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D018821:CD18 Antigens; D017127:Glycation End Products, Advanced; D024243:HMGB1 Protein; D018836:Inflammation Mediators; D039841:Leukocyte L1 Antigen Complex; D008024:Ligands; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D005947:Glucose