Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis

Bojana Stanic, Deepesh Pandey, David J Fulton, Francis J. Miller

Research output: Contribution to journalArticle

32 Citations (Scopus)

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. METHODS AND 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. CONCLUSION-: These data identify EGF-like ligands as potential modulators of atherogenesis, resulting in part from increased vascular NADPH oxidase activity.

Original languageEnglish (US)
Pages (from-to)2452-2460
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number10
DOIs
StatePublished - Nov 1 2012

Fingerprint

NADP
Epidermal Growth Factor
Primates
Blood Vessels
Atherosclerosis
Oxidoreductases
Ligands
Diet
Haplorhini
Arteries
Atherogenic Diet
Macaca fascicularis
Epidermal Growth Factor Receptor
Smooth Muscle Myocytes
Heparin
Macrophages
Membranes

Keywords

  • atherosclerosis
  • cell signaling
  • epidermal growth factor receptor
  • nicotinamide adenine dinucleotide phosphate oxidases
  • smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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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. METHODS AND 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. CONCLUSION-: These data identify EGF-like ligands as potential modulators of atherogenesis, resulting in part from increased vascular NADPH oxidase activity.",
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author = "Bojana Stanic and Deepesh Pandey and Fulton, {David J} and Miller, {Francis J.}",
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AU - Stanic, Bojana

AU - Pandey, Deepesh

AU - Fulton, David J

AU - Miller, Francis J.

PY - 2012/11/1

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