Chronic antioxidant supplementation attenuates nuclear factor-κB activation and preserves endothelial function in hypercholesterolemic pigs
Chronic antioxidant supplementation attenuates nuclear factor-κB activation and preserves endothelial function in hypercholesterolemic pigs
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DOI：
10.1016/s0008-6363(01)00535-1
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发表时间：
2002-03-01
影响因子：
10.8
通讯作者：
Lerman, A
中科院分区：
文献类型：
--
作者：
Rodriguez-Porcel, M;Lerman, LO;Lerman, A
目的：高胆固醇血症（HC）是一种促氧化状态，可激活核因子-κ B（NF-κ B），并与冠状动脉内皮功能障碍相关。体内慢性抗氧化干预对HC诱导的NF-κ B活化和冠状动脉内皮功能的生理意义尚不清楚。研究方法：在12周的正常饮食、伴随抗氧化剂干预的正常饮食（每天100 IU/kg的维生素E和I的维生素C）、2%HC饮食或HC饮食+抗氧化剂补充后，对四组猪进行了研究。通过Western印迹和清除剂活性和维生素E免疫组化水平研究NF-κ B活化和一氧化氮（NO）通路，同时通过冠状动脉组织自由基清除剂和C.血管内皮功能进行了研究，在体外冠状动脉血管反应性缓激肽和P物质。结果：HC动物增加了NF-κ B的激活，降低内皮NO合酶的表达，并减少自由基清除系统的活动，与受损的冠状动脉内皮功能。HC中的抗氧化剂补充使NF-κ B活化和NO生物活性正常化，并保护冠状动脉内皮功能。结论：本研究首次证明，在体内慢性中断内源性氧化应激级联减少HC诱导的NF-κ B活化和正常化NO生物活性与冠状动脉内皮功能的保护。这项研究表明，在早期动脉粥样硬化中氧化应激和NF κ B活化增加的作用。(C)2002 Elsevier Science B. V.保留所有权利。
Objective: Hypercholesterolemia (HC), a pro-oxidant condition, activates nuclear factor-kappa beta (NF-kappaB) and is associated with coronary endothelial dysfunction. The physiological significance of in vivo chronic antioxidant intervention on HC-induced NF-kappaB 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 I of vitamin C daily), 2% HC diet, or HC diet+ antioxidant supplementation. NF-kappaB activation and the nitric oxide (NO) pathway were investigated by Western blotting and scavenger activity and levels of vitamin E immunohistochemistry, while oxidative stress was evaluated by coronary artery tissue radical scavenger and C. Endothelial function was studied in vitro by coronary vasoreactivity to bradykinin and substance P. Results: HC animals had increased activation of NF-kappaB, decreased endothelial NO synthase expression, and decreased radical scavenger system activity, associated with impaired coronary endothelial function. Antioxidant supplementation in HC normalized NF-kappaB 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-kappaB activation and normalizes NO bioactivity in association with preservation of coronary endothelial function. This study suggests a role for increased oxidative stress and NFkappaB activation in early atherosclerosis. (C) 2002 Elsevier Science B.V. All rights reserved.