RAGE and its ligands: a lasting memory in diabetic complications?
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.
Yan
Shi-Fang
SF
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Ramasamy
Ravichandran
R
Bucciarelli
Loredana G
LG
Wendt
Thoralf
T
Lee
Larisse K
LK
Hudson
Barry I
BI
Stern
David M
DM
Lalla
Evanthia
E
DU Yan
Shi
S
Rong
Ling Ling
LL
Naka
Yoshifumi
Y
Schmidt
Ann Marie
AM
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
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