TY - JOUR
T1 - Chronic antioxidant supplementation attenuates nuclear factor-κB activation and preserves endothelial function in hypercholesterolemic pigs
AU - Rodriguez-Porcel, Martin
AU - Lerman, Lilach O.
AU - Holmes, David R.
AU - Richardson, Darcy
AU - Napoli, Claudio
AU - Lerman, Amir
N1 - Funding Information:
This work was supported by National Institutes of Health (grants HL 03621, HL 63282, and HL 63911), the Miami Heart Research Institute, the Bruce and Ruth Rappaport Program in Vascular Biology, the Mayo Foundation, and IS.NIH grant 56980 / 99. The authors are grateful to Paula Carlson, Drs Yang Lee and Filomena de Nigris for their technical support.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - Atherosclerosis
KW - Coronary circulation
KW - Endothelial function
KW - Free radicals
UR - http://www.scopus.com/inward/record.url?scp=0036197071&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036197071&partnerID=8YFLogxK
U2 - 10.1016/S0008-6363(01)00535-1
DO - 10.1016/S0008-6363(01)00535-1
M3 - Article
C2 - 11922911
AN - SCOPUS:0036197071
SN - 0008-6363
VL - 53
SP - 1010
EP - 1018
JO - Cardiovascular research
JF - Cardiovascular research
IS - 4
ER -