Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: insights into the pathogenesis of macrovascular complications in diabetes

• Published in: Current atherosclerosis reports Vol. 4; no. 3; pp. 228 - 237
• Main Authors: Wendt, Thoralf, Bucciarelli, Loredana, Qu, Wu, Lu, Yan, Yan, Shi Fang, Stern, David M, Schmidt, Ann Marie
• Format: Journal Article
• Language: English
• Published: United States 01-05-2002
• Subjects: Animals; Arteriosclerosis - chemically induced; Arteriosclerosis - immunology; Arteriosclerosis - metabolism; Diabetes Mellitus - immunology; Diabetes Mellitus - physiopathology; Diabetic Angiopathies - immunology; Diabetic Angiopathies - metabolism; Glycation End Products, Advanced - metabolism; Humans; Inflammation - complications; Inflammation - metabolism; Leukocyte L1 Antigen Complex - metabolism; Ligands; Membrane Proteins - metabolism; Mice; Models, Animal; Rats; Receptor for Advanced Glycation End Products; Receptors, Immunologic - metabolism; S100 Proteins - metabolism; Signal Transduction - physiology; Vascular Diseases - chemically induced; Vascular Diseases - metabolism
• ISSN: 1523-3804; 1534-6242
• DOI: 10.1007/s11883-002-0024-4

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.