RAGE axis: Animal models and novel insights into the vascular complications of diabetes.
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.
Naka
Yoshifumi
Y
Department of Surgery, College of Physicians & Surgeons, Columbia University, New York, NY 10032, USA.
Bucciarelli
Loredana G
LG
Wendt
Thoralf
T
Lee
Larisse K
LK
Rong
Ling Ling
LL
Ramasamy
Ravichandran
R
Yan
Shi Fang
SF
Schmidt
Ann Marie
AM
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D023903:Coronary Restenosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D003925:Diabetic Angiopathies / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006949:Hyperlipidemias / Q000097:blood / Q000150:complications / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000235:genetics / Q000502:physiology* / Q000627:therapeutic use; D015398:Signal Transduction; D012995:Solubility; D014657:Vasculitis / Q000378:metabolism* / Q000473:pathology
D001057:Apolipoproteins E; D015815:Cell Adhesion Molecules; D016207:Cytokines; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic