{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T16:22:32Z","timestamp":1791390152687,"version":"4.3.3"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,3,10]]},"abstract":"\n \n Background\u2014<\/jats:italic>\n <\/jats:bold>\n We tested the hypothesis that nuclear factor-\u03baB (NF-\u03baB) activity contributes to vascular endothelial dysfunction with aging and obesity in humans.\n <\/jats:p>\n \n \n Methods and Results\u2014<\/jats:italic>\n <\/jats:bold>\n We conducted a randomized, double-blind, placebo-controlled crossover study in 14 nondiabetic overweight or obese (body mass index \u226525 kg\/m\n 2<\/jats:sup>\n ) middle-aged and older (age 52 to 68 years) adults. Salsalate (nonacetylated salicylate, 4500 mg\/d), a compound that inhibits NF-\u03baB activity, or placebo was administered for 4-day periods. Plasma salicylate concentrations reached the midtherapeutic range (21.8\u00b11.1 mg\/100 mL,\n P<\/jats:italic>\n \u22640.0001 versus placebo) by day 4 of salsalate treatment. Salsalate increased expression of the inhibitor of NF-\u03baB and reduced total and nuclear expression of NF-\u03baB in endothelial cells obtained from the subjects (all\n P<\/jats:italic>\n <0.05). Salsalate increased brachial artery flow-mediated dilation by 74% (from 4.0\u00b10.4% to 6.6\u00b10.5%,\n P<\/jats:italic>\n <0.001) but did not affect endothelium-independent dilation (\n P<\/jats:italic>\n =0.83). The change in brachial artery flow-mediated dilation with salsalate was inversely related to baseline flow-mediated dilation (\n r<\/jats:italic>\n =\u22120.77,\n P<\/jats:italic>\n <0.01). Infusion of vitamin C increased brachial artery flow-mediated dilation during placebo (\n P<\/jats:italic>\n <0.001) but not after salsalate (\n P<\/jats:italic>\n =0.23). Salsalate reduced nitrotyrosine (\n P<\/jats:italic>\n =0.06) and expression of NADPH oxidase p47\n phox<\/jats:sup>\n (\n P<\/jats:italic>\n <0.05) in endothelial cells obtained from the subjects but did not influence circulating or endothelial cell inflammatory proteins.\n <\/jats:p>\n \n \n Conclusions\u2014<\/jats:italic>\n <\/jats:bold>\n Our findings provide the first direct evidence that NF-\u03baB, 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.\n <\/jats:p>","DOI":"10.1161\/circulationaha.108.804294","type":"journal-article","created":{"date-parts":[[2009,2,23]],"date-time":"2009-02-23T21:11:02Z","timestamp":1235423462000},"page":"1284-1292","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":234,"title":["Nuclear Factor-\u03baB Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight\/Obese Middle-Aged and Older Humans"],"prefix":"10.1161","volume":"119","author":[{"given":"Gary L.","family":"Pierce","sequence":"first","affiliation":[{"name":"From the Department of Integrative Physiology, University of Colorado, Boulder."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa A.","family":"Lesniewski","sequence":"additional","affiliation":[{"name":"From the Department of Integrative Physiology, University of Colorado, Boulder."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke R.","family":"Lawson","sequence":"additional","affiliation":[{"name":"From the Department of Integrative Physiology, University of Colorado, Boulder."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacy D.","family":"Beske","sequence":"additional","affiliation":[{"name":"From the Department of Integrative Physiology, University of Colorado, Boulder."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R.","family":"Seals","sequence":"additional","affiliation":[{"name":"From the Department of Integrative Physiology, University of Colorado, Boulder."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000048892.83521.58"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199801013380101"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118709"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.572"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000020401.61826.ea"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-1049fje"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.1.159"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.179.2.503"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.10.3961"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01346.2006"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2007.05.016"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.106.657486"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.0000269183.13937.e8"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2008.00438.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8052854"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/23948"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.17.2022"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000161818.28974.1a"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1152\/jappl.1998.84.1.372"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.12.1351"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00660.2006"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2005.102566"},{"key":"e_1_3_2_23_2","first-page":"215","volume":"556","year":"2004","unstructured":"Eskurza I, Monahan K, Robinson J, Seals DR. 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