RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes.
Although the underlying causes of hyperglycemia are multiple, a common thread associated with high levels of blood sugar is the development of a range of vascular and inflammatory complications that might seriously limit the quality and duration of life in affected individuals. Despite multiple aggressive efforts to prevent complications, diabetes remains the leading disease consuming healthcare dollars in the USA. This review focuses on the role of advanced glycation endproducts (AGEs) and their interaction with their signal-transduction AGE receptor (RAGE), in vascular and inflammatory cell perturbation and the chronic activation that underlies diabetes. Our studies provide mechanistic insights into complications within the macrovasculature and those ensuing from an exaggerated host response to invading bacteria, and suggest that blockade of RAGE might provide a potent and safe strategy for the prevention of complications that typify long-term diabetes.
Schmidt
A M
AM
College of Physicians & Surgeons, 630 West 168th Street, P&S 17-501, Columbia University, New York, NY 10032, USA. ams11@columbia.edu
Stern
D M
DM
D000818:Animals; D048909:Diabetes Complications; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic