Journal article
Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: possible role of nuclear factor kappa B
Clinical science (1979), Vol.127(11-12), pp.645-654
12/01/2014
DOI: 10.1042/CS20140030
PMCID: PMC4408779
PMID: 24947434
Abstract
Habitual aerobic exercise prevents age-related impairments in endothelium-dependent dilation (EDD). We have hypothesized that the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappa B) impairs EDD with sedentary aging, and habitual aerobic exercise prevents this age-related suppression of EDD by NF-kappa B. To test this hypothesis, we have inhibited NF-kappa B signalling via oral salsalate administration in healthy older aerobic exercise-trained adults (OT, n = 14, 58 +/- 2 years), older non-exercising adults (ON, n = 16, 61 +/- 1 years) and young non-exercising controls (YN, n = 8, 23 +/- 1 years). Salsalate reduced endothelial cell expression of NE-kappa B p65 by similar to 25% in ON (P < 0.05) but did not significantly change expression in OT or YN (P > 0.05). EDD, assessed by brachial artery flow-mediated dilation (FMD), was improved by salsalate in ON (4.0 +/- 0.7% compared with 6.8 +/- 0.7%, placebo compared with salsalate, P < 0.001) but did not change with salsalate in OT or YN (OT: 7.2 +/- 0.7% compared with 7.7 +/- 0.6%; YN: 7.6 +/- 0.9% compared with 8.1 +/- 0.8%; placebo compared with salsalate, P > 0.05). Endothelium-independent dilation was not affected by salsalate in any group (P > 0.05). In ON, vitamin C infusion improved FMD by 30% during placebo (P < 0.001) but had no affect during salsalate (P > 0.05). In OT and YN, vitamin C infusion did not affect FMD during either placebo or salsalate (P > 0.05). Salsalate reduced endothelial cell nitrotyrosine content by similar to 25% and NADPH oxidase p47(phox) expression by similar to 30% in ON (P < 0.05) but had no effect in OT or YN (P > 0.05). Our results suggest that endothelial NF-kappa B signalling is associated with oxidative stress-related impairment of EDD in healthy non-exercising but not aerobically exercising older adults. This may be a key mechanism by which regular aerobic exercise preserves endothelial function and reduces cardiovascular risk with aging.
Details
- Title: Subtitle
- Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: possible role of nuclear factor kappa B
- Creators
- Ashley E. Walker - University of Colorado BoulderRachelle E. Kaplon - University of Colorado BoulderGary L. Pierce - University of Colorado BoulderMolly J. Nowlan - University of Colorado BoulderDouglas R. Seals - University of Colorado Boulder
- Resource Type
- Journal article
- Publication Details
- Clinical science (1979), Vol.127(11-12), pp.645-654
- DOI
- 10.1042/CS20140030
- PMID
- 24947434
- PMCID
- PMC4408779
- NLM abbreviation
- Clin Sci (Lond)
- ISSN
- 0143-5221
- eISSN
- 1470-8736
- Publisher
- Portland Press Ltd
- Number of pages
- 10
- Grant note
- T32AG000279 / NATIONAL INSTITUTE ON AGING; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA) 0715735Z / American Heart Association UL1TR000154 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) P30DK048520 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) AG031617; AG006537; AG013038; AG022241; AG000279; TR000154 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 12/01/2014
- Academic Unit
- Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984267138002771
Metrics
8 Record Views