Journal article
Nuclear Factor-κB Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight/Obese Middle-Aged and Older Humans
Circulation (New York, N.Y.), Vol.119(9), pp.1284-1292
03/10/2009
DOI: 10.1161/CIRCULATIONAHA.108.804294
PMCID: PMC2810548
PMID: 19237660
Abstract
Background: We tested the hypothesis that nuclear factor-kappaB (NF-kappaB) 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 > or =25 kg/m(2)) middle-aged and older (age 52 to 68 years) adults. Salsalate (nonacetylated salicylate, 4500 mg/d), a compound that inhibits NF-kappaB activity, or placebo was administered for 4-day periods. Plasma salicylate concentrations reached the midtherapeutic range (21.8+/-1.1 mg/100 mL, P< or =0.0001 versus placebo) by day 4 of salsalate treatment. Salsalate increased expression of the inhibitor of NF-kappaB and reduced total and nuclear expression of NF-kappaB 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 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-kappaB, 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.
Details
- Title: Subtitle
- Nuclear Factor-κB Activation Contributes to Vascular Endothelial Dysfunction via Oxidative Stress in Overweight/Obese Middle-Aged and Older Humans
- Creators
- Gary L Pierce - From the Department of Integrative Physiology, University of Colorado, BoulderLisa A Lesniewski - From the Department of Integrative Physiology, University of Colorado, BoulderBrooke R Lawson - From the Department of Integrative Physiology, University of Colorado, BoulderStacy D Beske - From the Department of Integrative Physiology, University of Colorado, BoulderDouglas R Seals - From the Department of Integrative Physiology, University of Colorado, Boulder
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.119(9), pp.1284-1292
- DOI
- 10.1161/CIRCULATIONAHA.108.804294
- PMID
- 19237660
- PMCID
- PMC2810548
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 03/10/2009
- Academic Unit
- Health and Human Physiology; Internal Medicine
- Record Identifier
- 9984002348102771
Metrics
22 Record Views