title: RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice.
abstract: BACKGROUND
  Previous studies suggested that blockade of RAGE in diabetic apolipoprotein (apo) E-null mice suppressed early acceleration of atherosclerosis. A critical test of the potential applicability of RAGE blockade to clinical settings was its ability to impact established vascular disease. In this study, we tested the hypothesis that RAGE contributed to lesion progression in established atherosclerosis in diabetic apoE-null mice.
  
  
  RESULTS
  Male apoE-null mice, age 6 weeks, were rendered diabetic with streptozotocin or treated with citrate buffer. At age 14 weeks, certain mice were killed or treated with once-daily murine soluble RAGE or albumin; all mice were killed at age 20 weeks. Compared with diabetic mice at age 14 weeks, albumin-treated animals displayed increased atherosclerotic lesion area and complexity. In diabetic mice treated with sRAGE from age 14 to 20 weeks, lesion area and complexity were significantly reduced and not statistically different from those observed in diabetic mice at age 14 weeks. In parallel, decreased parameters of inflammation and mononuclear phagocyte and smooth muscle cell activation were observed.
  
  
  CONCLUSIONS
  RAGE contributes not only to accelerated lesion formation in diabetic apoE-null mice but also to lesion progression. Blockade of RAGE may be a novel strategy to stabilize atherosclerosis and vascular inflammation in established diabetes.
authors.affiliation: Division of Surgical Science, College of Physicians & Surgeons, Department of Surgery, Columbia University, New York, NY 10032, USA.
authors.forename: Loredana G
authors.initials: LG
authors.lastname: Bucciarelli
authors.forename: Thoralf
authors.initials: T
authors.lastname: Wendt
authors.forename: Wu
authors.initials: W
authors.lastname: Qu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Evanthia
authors.initials: E
authors.lastname: Lalla
authors.forename: Ling Ling
authors.initials: LL
authors.lastname: Rong
authors.forename: Mouza T
authors.initials: MT
authors.lastname: Goova
authors.forename: Bernhard
authors.initials: B
authors.lastname: Moser
authors.forename: Thomas
authors.initials: T
authors.lastname: Kislinger
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Lee
authors.forename: Yogita
authors.initials: Y
authors.lastname: Kashyap
authors.forename: David M
authors.initials: DM
authors.lastname: Stern
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications*; D004195:Disease Models, Animal; D018450:Disease Progression; D007274:Injections, Intraperitoneal; D007963:Leukocytes, Mononuclear / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D010586:Phagocytes / Q000473:pathology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000008:administration & dosage* / Q000037:antagonists & inhibitors*; D012850:Sinus of Valsalva / Q000187:drug effects / Q000473:pathology; D013311:Streptozocin; D016896:Treatment Outcome; D014657:Vasculitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology
chemical_list: D001057:Apolipoproteins E; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D013311:Streptozocin