title: Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclerosis.
abstract: BACKGROUND
  Cardiovascular ischemic events may occur more frequently in hypertensive patients with activated renin-angiotensin systems. We tested the hypothesis that angiotensin II (Ang II) may contribute to atherosclerosis by increasing expression of vascular inflammatory genes such as vascular cell adhesion molecule-1 (VCAM-1).
  
  
  RESULTS
  Rats infused with norepinephrine or Ang II for 6 days developed similar hypertensive responses, but only Ang II-treated rats exhibited significant increases in aortic VCAM-1 protein and mRNA expression. Oral losartan treatment (50 mg. kg(-1). d(-1)) inhibited Ang II-induced hypertension and aortic VCAM-1 mRNA expression. Ang II treatment significantly increased VCAM-1 mRNA expression in cultured rat aortic smooth muscle cells (RASMCs). Ang II also induced nuclear NF-kappaB-like binding activity and transactivated an NF-kappaB-driven VCAM-1 promoter. Losartan and proteasome inhibitors blocked Ang II-induced NF-kappaB activation and VCAM-1 mRNA accumulation. IkappaB-alpha overexpression in RASMCs inhibited Ang II-induced VCAM-1 promoter transactivation.
  
  
  CONCLUSIONS
  Ang II may contribute to atherogenesis by activation of VCAM-1 through proteasome dependent, NF-kappaB-like transcriptional mechanisms.
authors.affiliation: Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Tummala
authors.forename: X L
authors.initials: XL
authors.lastname: Chen
authors.forename: C L
authors.initials: CL
authors.lastname: Sundell
authors.forename: J B
authors.initials: JB
authors.lastname: Laursen
authors.forename: C P
authors.initials: CP
authors.lastname: Hammes
authors.forename: R W
authors.initials: RW
authors.lastname: Alexander
authors.forename: D G
authors.initials: DG
authors.lastname: Harrison
authors.forename: R M
authors.initials: RM
authors.lastname: Medford
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001161:Arteriosclerosis / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D011945:Receptors, Angiotensin; D019010:Vascular Cell Adhesion Molecule-1; D000804:Angiotensin II; D009638:Norepinephrine