title: Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis.
abstract: OBJECTIVE
  To characterize the relationship between the expression of epidermal growth factor (EGF)-like ligands and vascular nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression and activity in a primate model of atherosclerosis.
  
  
  RESULTS
  Adult male Cynomolgus monkeys were fed a normal or atherogenic (AS) diet for 45 months, after which animals from the AS group were placed on a normal diet for 8 months (regression). The expression of membrane-associated EGF-like ligands was increased in arteries from animals on the AS diet and normalized in the regression group. EGF-like ligands were distributed throughout atherosclerotic vessels but predominantly colocalized with macrophages. Consistent with ligand shedding, circulating heparin-bound EGF was elevated in the plasma of AS monkeys but not in those on regression diet. Atherosclerosis was associated with the activation of EGF receptor signaling. Expression of NADPH oxidase subunits Nox1 and Nox2 but not Nox4 or Nox5 was increased in arteries from monkeys on the AS diet and returned to normal with regression. Levels of Nox1 and Nox2 positively correlated with EGF-like ligands. In cultured monkey smooth muscle cells, treatment with EGF-like ligands increased Nox1 expression and activity.
  
  
  CONCLUSIONS
  These data identify EGF-like ligands as potential modulators of atherogenesis, resulting in part from increased vascular NADPH oxidase activity.
authors.affiliation: Department of Internal Medicine The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Bojana
authors.initials: B
authors.lastname: Stanic
authors.forename: Deepesh
authors.initials: D
authors.lastname: Pandey
authors.forename: David J
authors.initials: DJ
authors.lastname: Fulton
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Miller
mesh_terms: D000818:Animals; D001158:Arteries / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004036:Diet, Atherogenic / Q000009:adverse effects; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism*; D008024:Ligands; D008252:Macaca fascicularis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D019255:NADPH Oxidases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D008024:Ligands; D004815:Epidermal Growth Factor; D019255:NADPH Oxidases