Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: Possible role of nuclear factor-κB

摘要

Habitual aerobic exercise prevents age-related impairments in endothelium-dependent dilation (EDD). We hypothesized that the pro-inflammatory transcription factor nuclear factor κB (NF-κB) impairs EDD with sedentary aging and habitual aerobic exercise prevents this age-related suppression of EDD by NF-κB. To test this hypothesis, we inhibited NF-κB signaling 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 NF-κB p65 by ~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% vs. 6.8±0.7%, placebo vs. salsalate, P<0.001), but did not change with salsalate in OT or YN (OT: 7.2±0.7% vs. 7.7±0.6%; YN: 7.6±0.9% vs. 8.1±0.8%; placebo vs. 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 ~25% and NADPH oxidase p47^phox expression by ~30% in ON (P<0.05), but had no effect in OT or YN (P>0.05). Our results suggest that endothelial NF-κB signaling 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.