Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes.
The incidence and severity of atherosclerosis is increased in patients with diabetes. Indeed, accelerated macrovascular disease in diabetic patients has emerged as a leading cause of morbidity and mortality in the United States and worldwide. Multiple investigations have suggested that there are numerous potential contributory factors that underlie these observations. Our laboratory has focused on the contribution of receptor for advanced glycation endproducts (RAGE) and its proinflammatory ligands, advanced glycation endproducts (AGEs) and S100/calgranulins in vascular perturbation, manifested as enhanced atherogenesis or accelerated restenosis after angioplasty. In rodent models of diabetic complications, blockade of RAGE suppressed vascular hyperpermeability, accelerated atherosclerotic lesion area and complexity in diabetic apolipoprotein E-deficient mice, and prevented exaggerated neointimal formation in hyperglycemic fatty Zucker rats subjected to injury of the carotid artery. In this review, we summarize these findings and provide an overview of distinct mechanisms that contribute to the development of accelerated diabetic macrovascular disease. Insights into therapeutic strategies to prevent or interrupt these processes are presented.
Wendt
Thoralf
T
Division of Surgical Science, Department of Surgery, Columbia University College of Physicians & Surgeons, 630 West 168th Street, P&S 17-401, New York, NY 10032, USA.
Bucciarelli
Loredana
L
Qu
Wu
W
Lu
Yan
Y
Yan
Shi Fang
SF
Stern
David M
DM
Schmidt
Ann Marie
AM
D000818:Animals; D001161:Arteriosclerosis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D003920:Diabetes Mellitus / Q000276:immunology / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000276:immunology / Q000378:metabolism*; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D023421:Models, Animal; D051381:Rats; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D009418:S100 Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014652:Vascular Diseases / Q000139:chemically induced / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D039841:Leukocyte L1 Antigen Complex; D008024:Ligands; D008565:Membrane Proteins; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins