Published online before print May 20, 2004, doi: 10.1161/01.ATV.0000133191.71196.90
© 2004 American Heart Association, Inc.
Brief Reviews |
RAGE Axis
Animal Models and Novel Insights Into the Vascular Complications of Diabetes
From the Department of Surgery, College of Physicians & Surgeons, Columbia University, New York, NY.
Correspondence to Dr Ann Marie Schmidt, Division of Surgical Science, Department of Surgery, College of Physicians & Surgeons, Columbia University, 630 West 168th Street, P&S 17-501, New York, NY 10032. E-mail ams11{at}columbia.edu
Series Editor: Richard A. Cohen
ATVB In Focus
Diabetic Vascular Disease: Pathophysiological Mechanisms in the Diabetic Milieu and Therapeutic Implications
Receptor for AGE (RAGE) is a multi-ligand member of the immunoglobulin superfamily of cell surface molecules. Engagement of RAGE by its signal transduction ligands evokes inflammatory cell infiltration and activation in the vessel wall. In diabetes, when fueled by oxidant stress, hyperglycemia, and superimposed stresses such as hyperlipidemia or acute balloon/endothelial denuding arterial injury, the ligand–RAGE axis amplifies vascular stress and accelerates atherosclerosis and neointimal expansion. In this brief synopsis, we review the use of rodent models to test these concepts. Taken together, our findings support the premise that RAGE is an amplification step in vascular inflammation and acceleration of atherosclerosis. Future studies must rigorously test the potential impact of RAGE blockade in human subjects; such trials are on the horizon.
Ligand engagement of the receptor for advanced glycation end products (RAGE) evokes vascular inflammation and perturbation. In diabetes, when fueled by oxidation, hyperglycemia, and superimposed stresses, the ligand–RAGE axis accelerates atherosclerosis and neointimal expansion. Studies in rodent models of diabetes suggest that testing the impact of RAGE blockade in human subjects is logical.
Key Words: diabetes • animal models • receptors • inflammation • signal transduction
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