Chronic antioxidant supplementation attenuates nuclear factor-κB activation and preserves endothelial function in hypercholesterolemic pigs

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Objective: Hypercholesterolemia (HC), a pro-oxidant condition, activates nuclear factor-kappa beta (NF-κB) and is associated with coronary endothelial dysfunction. The physiological significance of in vivo chronic antioxidant intervention on HC-induced NF-κB activation and coronary endothelial function remains unclear. Methods: Four groups of pigs were studied after 12 weeks of normal diet, normal diet with concomitant antioxidant intervention (100 IU/kg of vitamin E and 1 g of vitamin C daily), 2% HC diet, or HC diet+antioxidant supplementation. NF-κB activation and the nitric oxide (NO) pathway were investigated by Western blotting and immunohistochemistry, while oxidative stress was evaluated by coronary artery tissue radical scavenger activity and levels of vitamin E and C. Endothelial function was studied in vitro by coronary vasoreactivity to bradykinin and substance P. Results: HC animals had increased activation of NF-κB, decreased endothelial NO synthase expression, and decreased radical scavenger system activity, associated with impaired coronary endothelial function. Antioxidant supplementation in HC normalized NF-κB activation and NO bioactivity, and preserves coronary endothelial function. Conclusions: This study demonstrates for the first time that in vivo chronic interruption of the endogenous oxidative stress cascade reduces HC-induced NF-κB activation and normalizes NO bioactivity in association with preservation of coronary endothelial function. This study suggests a role for increased oxidative stress and NFκB activation in early atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1010-1018
Number of pages9
JournalCardiovascular research
Volume53
Issue number4
DOIs
StatePublished - Apr 9 2002

Keywords

  • Atherosclerosis
  • Coronary circulation
  • Endothelial function
  • Free radicals

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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