title: Angiotensin II amplifies macrophage-driven atherosclerosis.
abstract: OBJECTIVE
  We evaluated the role of angiotensin II (AII) in a marrow-derived macrophage-driven model of atherosclerosis.
  
  
  RESULTS
  Eight-week-old C57BL/6 wild-type mice were reconstituted with bone marrow harvested from apolipoprotein E-deficient (apoE-/---> apoE+/+) or wild-type for apoE gene (apoE+/+--> apoE+/+) mice. At 20 weeks, mice were exposed to either AII (1000 ng/kg per minute subcutaneously) or saline for 2 weeks. Animals did not differ in body weight, blood pressure, cholesterol/triglycerides, or peripheral blood monocyte counts. ApoE-/---> apoE+/+ mice exposed to AII had 3-fold greater atherosclerotic area than saline-treated apoE-/---> apoE+/+ mice. By contrast, AII did not affect atherosclerosis in apoE+/+--> apoE+/+ mice. Macrophage-positive areas were increased by AII in mice reconstituted with either apoE-deficient or apoE-competent marrow. AII also significantly increased fragmentation of elastin laminae in both apoE-/---> apoE+/+ and apoE+/+--> apoE+/+ mice. In vitro, AII caused greater increase in monocyte chemoattractant protein-1-stimulated migration of macrophages harvested from AII-infused versus saline-infused mice.
  
  
  CONCLUSIONS
  The current studies reveal that AII has both initiating and sustaining proatherogenic effects. By promoting macrophage migration into the vascular intima, AII is pivotal in initiating atherosclerosis; by promoting elastin breaks, a novel mechanism implicated in migration and proliferation of smooth muscle cells, AII may be pivotal in subsequent development and expansion of atherosclerotic lesion.
authors.affiliation: Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tenn, USA.
authors.forename: Ayabe
authors.initials: A
authors.lastname: Nobuhiko
authors.forename: Eisuke
authors.initials: E
authors.lastname: Suganuma
authors.forename: Vladimir R
authors.initials: VR
authors.lastname: Babaev
authors.forename: Agnes
authors.initials: A
authors.lastname: Fogo
authors.forename: Larry L
authors.initials: LL
authors.lastname: Swift
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.forename: Iekuni
authors.initials: I
authors.lastname: Ichikawa
authors.forename: Valentina
authors.initials: V
authors.lastname: Kon
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000502:physiology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D002784:Cholesterol / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015918:Infusion Pumps, Implantable; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001057:Apolipoproteins E; D000804:Angiotensin II; D002784:Cholesterol