TY - JOUR
T1 - RAGE axis
T2 - Animal models and novel insights into the vascular complications of diabetes
AU - Naka, Yoshifumi
AU - Bucciarelli, Loredana G.
AU - Wendt, Thoralf
AU - Lee, Larisse K.
AU - Ling, Ling Rong
AU - Ramasamy, Ravichandran
AU - Shi, Fang Yan
AU - Schmidt, Ann Marie
PY - 2004/8
Y1 - 2004/8
N2 - 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.
AB - 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.
KW - Animal models
KW - Diabetes
KW - Inflammation
KW - Receptors
KW - Signal transduction
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U2 - 10.1161/01.ATV.0000133191.71196.90
DO - 10.1161/01.ATV.0000133191.71196.90
M3 - Article
C2 - 15155381
AN - SCOPUS:3943061592
VL - 24
SP - 1342
EP - 1349
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 8
ER -