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RAGE and its ligands: a lasting memory in diabetic complications?Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Medical College of Georgia, Augusta, Georgia, US
Division of Periodontics, School of Dental and Oral Surgery, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US
Departments of Surgery and Pathology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, US 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.
Key Words: receptor for advanced glycation end products (RAGE) • S100/calgranulins • amphoterin • mononuclear phagocytes • glycaemic memory
Diabetes and Vascular Disease Research, Vol. 1, No. 1,
10-20 (2004) This article has been cited by other articles:
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