Nuclear Factor-kappaB Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight/Obese Middle-Aged and Older Humans Export

@article{citeulike:4156293, abstract = {Background-- We tested the hypothesis that nuclear factor-{kappa}B (NF-{kappa}B) 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 [\&ge;]25 kg/m2) middle-aged and older (age 52 to 68 years) adults. Salsalate (nonacetylated salicylate, 4500 mg/d), a compound that inhibits NF-{kappa}B activity, or placebo was administered for 4-day periods. Plasma salicylate concentrations reached the midtherapeutic range (21.8{+/-}1.1 mg/100 mL, P[\&le;]0.0001 versus placebo) by day 4 of salsalate treatment. Salsalate increased expression of the inhibitor of NF-{kappa}B and reduced total and nuclear expression of NF-{kappa}B in endothelial cells obtained from the subjects (all P<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 (P<0.001) but not after salsalate (P=0.23). Salsalate reduced nitrotyrosine (P=0.06) and expression of NADPH oxidase p47phox (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-{kappa}B, 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. 10.1161/CIRCULATIONAHA.108.804294}, author = {Pierce, Gary L. and Lesniewski, Lisa A. and Lawson, Brooke R. and Beske, Stacy D. and Seals, Douglas R.}, citeulike-article-id = {4156293}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/CIRCULATIONAHA.108.804294}, citeulike-linkout-1 = {http://circ.ahajournals.org/cgi/content/abstract/119/9/1284}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19237660}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19237660}, day = {10}, doi = {10.1161/CIRCULATIONAHA.108.804294}, journal = {Circulation}, keywords = {endothelial\_cells, endothelial\_dysfunction, flow\_mediated\_dilation, nf\_kappa, obesity, salicylate, salsalate}, month = {March}, number = {9}, pages = {1284--1292}, posted-at = {2009-10-13 18:19:29}, priority = {2}, title = {Nuclear Factor-{kappa}B Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight/Obese Middle-Aged and Older Humans}, url = {http://dx.doi.org/10.1161/CIRCULATIONAHA.108.804294}, volume = {119}, year = {2009} }

TY - JOUR ID - citeulike:4156293 L3 - citeulike-article-id:4156293 N2 - Background-- We tested the hypothesis that nuclear factor-{kappa}B (NF-{kappa}B) 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 [&ge;]25 kg/m2) middle-aged and older (age 52 to 68 years) adults. Salsalate (nonacetylated salicylate, 4500 mg/d), a compound that inhibits NF-{kappa}B activity, or placebo was administered for 4-day periods. Plasma salicylate concentrations reached the midtherapeutic range (21.8{+/-}1.1 mg/100 mL, P[&le;]0.0001 versus placebo) by day 4 of salsalate treatment. Salsalate increased expression of the inhibitor of NF-{kappa}B and reduced total and nuclear expression of NF-{kappa}B in endothelial cells obtained from the subjects (all P<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 (P<0.001) but not after salsalate (P=0.23). Salsalate reduced nitrotyrosine (P=0.06) and expression of NADPH oxidase p47phox (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-{kappa}B, 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. 10.1161/CIRCULATIONAHA.108.804294 IS - 9 JF - Circulation EP - 1292 TI - Nuclear Factor-{kappa}B Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight/Obese Middle-Aged and Older Humans VL - 119 SP - 1284 KW - endothelial_cells KW - endothelial_dysfunction KW - flow_mediated_dilation KW - nf_kappa KW - obesity KW - salicylate KW - salsalate AU - Pierce, Gary AU - Lesniewski, Lisa AU - Lawson, Brooke AU - Beske, Stacy AU - Seals, Douglas PY - 2009/03/10/ UR - http://dx.doi.org/10.1161/CIRCULATIONAHA.108.804294 ER -