|
 |
|||||||||||||||||||
|
|||||||||||||||||||
|
|||||||||||||||||||
 |
 |
|
|
Fundamental Roles in the Inflammatory Response: Winding the Way to the Pathogenesis of Endothelial Dysfunction and Atherosclerosis
Departments of a Surgery and c Medicine, Columbia University Medical Center, New York, New York, USA b Department of Medicine and Immunobiology, Yale University School of Medicine, New Haven, Connecticut, USA
Key Words: receptor for advanced glycation end products • inflammation • atherosclerosis • adaptive immunity • T cell priming
Address for correspondence: Dr. Ann Marie Schmidt, Department of Surgery, Columbia University Medical Center, 630 West 168th Street, P&S 17-401, New York, NY 10032. Voice: +1-212 305 6406; fax: +1-212 305 5337. ams11{at}columbia.edu
The multiligand receptor for advanced glycation end products (RAGE) of the immunoglobulin superfamily is expressed on multiple cell types implicated in the immune–inflammatory response and in atherosclerosis. Multiple studies have elucidated that ligand–RAGE interaction on cells, such as monocytes, macrophages, and endothelial cells, mediates cellular migration and upregulation of proinflammatory and prothrombotic molecules. In addition, recent studies reveal definitive rules for RAGE in effective T lymphocyte priming in vivo. RAGE ligand AGEs may be formed in diverse settings; although AGEs are especially generated in hyperglycemia, their production in settings characterized by oxidative stress and inflammation suggests that these species, in part via RAGE, may contribute to the pathogenesis of atherosclerosis. In murine models of atherosclerosis, vascular inflammation is a key factor and one which is augmented, in parallel with even further increases in RAGE ligands, in diabetic macrovessels. The findings that antagonism and genetic disruption of RAGE in atherosclerosis-susceptible mice strikingly reduces vascular inflammation and atherosclerotic lesion area and complexity link RAGE intimately to these processes and suggest that RAGE is a logical target for therapeutic intervention in aberrant inflammatory mechanisms and in atherosclerosis.
|
 |
 |
