Skip Navigation

Cardiovascular Research 2002 53(4):1010-1018; doi:10.1016/S0008-6363(01)00535-1
© 2002 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Rodriguez-Porcel, M.
Right arrow Articles by Lerman, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rodriguez-Porcel, M.
Right arrow Articles by Lerman, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 2002, European Society of Cardiology

Chronic antioxidant supplementation attenuates nuclear factor-{kappa}B activation and preserves endothelial function in hypercholesterolemic pigs

Martin Rodriguez-Porcela, Lilach O Lermanb, David R Holmes, Jr.a, Darcy Richardsona, Claudio Napolic,d and Amir Lermana,*

aDepartment of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
bDepartment of Internal Medicine, Division of Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA
cDepartment of Medicine, University of Naples, Naples, Italy
dDepartment of Medicine—0682, University of California, San Diego, CA, USA

* Corresponding author. Tel.: +1-507-255-4152; fax: +1-507-255-2550 lerman.amir{at}mayo.edu

Objective: Hypercholesterolemia (HC), a pro-oxidant condition, activates nuclear factor-kappa beta (NF-{kappa}B) and is associated with coronary endothelial dysfunction. The physiological significance of in vivo chronic antioxidant intervention on HC-induced NF-{kappa}B 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-{kappa}B 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-{kappa}B, decreased endothelial NO synthase expression, and decreased radical scavenger system activity, associated with impaired coronary endothelial function. Antioxidant supplementation in HC normalized NF-{kappa}B 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-{kappa}B activation and normalizes NO bioactivity in association with preservation of coronary endothelial function. This study suggests a role for increased oxidative stress and NF{kappa}B activation in early atherosclerosis.

KEYWORDS Atherosclerosis; Coronary circulation; Endothelial function; Free radicals


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.