The ligand/RAGE axis: lighting the fuse and igniting vascular stress.
Vascular inflammation contributes critically to the initiation and progression of atherosclerosis. These processes are accelerated in hyperglycemia and play key roles in the increased incidence and severity of myocardial infarction and stroke observed in diabetes. Evidence suggests that the ligands of the receptor for advanced glycation endproducts (RAGE), a multiligand member of the immunoglobulin superfamily, interact with this receptor to play important roles in both early development and progression of atherosclerosis and vascular inflammation. Studies in animal models of vascular injury underscored the potent impact of RAGE blockade; administration of ligand-binding decoys of RAGE or antibodies to the receptor reduced the consequences of diabetes, hyperlipidemia, and physical injury to the vessel wall. This review focuses on the ligand repertoire of RAGE, the impact of ligand-RAGE interaction, and the potent effect of RAGE blockade in rodent models of vascular injury.
Yan
Shi Fang
SF
Division of Surgical Science, Department of Surgery, Columbia University Medical Center, 630 West 168th Street, P&S 17-501, New York, NY 10032, USA.
Naka
Yoshifumi
Y
Hudson
Barry I
BI
Herold
Kevan
K
Yan
Shi Du
SD
Ramasamy
Ravichandran
R
Schmidt
Ann Marie
AM
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D004195:Disease Models, Animal; D017127:Glycation End Products, Advanced / Q000737:chemistry*; D006801:Humans; D007249:Inflammation; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D014652:Vascular Diseases / Q000473:pathology* / Q000628:therapy*
D016229:Amyloid beta-Peptides; D017127:Glycation End Products, Advanced; D008024:Ligands