Nuclear factor-κB activation contributes to vascular endothelial dysfunction via oxidative stress in overweight/obese middle-aged and older humans

Abstract

Background-We tested the hypothesis that nuclear factor-κB (NF-κB) activity contributes to vascular endothelial dysfunction with aging and obesity in humans. Methods and Results-We conducted a randomized, double-blind, placebo-controlled crossover study in 14 nondiabetic overweight or obese (body mass index ≥25 kg/m <0.05). Salsalate increased brachial artery flow-mediated dilation by 74% (from 4.0±0.4% to 6.6±0.5%, P<0.001) but did not affect endothelium-independent dilation (P=0.83). The change in brachial artery flow-mediated dilation with salsalate was inversely related to baseline flow-mediated dilation (r=-0.77, P<0.01). Infusion of vitamin C increased brachial artery flow-mediated dilation during placebo (F<0.001) but not after salsalate (P=0.23). Salsalate reduced nitrotyrosine (F=0.06) and expression of NADPH oxidase p47 phox (P<0.05) in endothelial cells obtained from the subjects but did not influence circulating or endothelial cell inflammatory proteins. Conclusions-Our findings provide the first direct evidence that NF-κB, in part via stimulation of oxidative stress, plays an important role in mediating vascular endothelial dysfunction in overweight and obese middle-aged and older humans. © 2009 American Heart Association, Inc.