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Absence of nuclear factor κB‐mediated suppression of vascular endothelial function with aging in exercising adults
Author(s) -
Walker Ashley E,
Pierce Gary L,
Kaplon Rachelle E,
Russell Molly J,
Lesniewski Lisa A,
Donato Anthony J,
Seals Douglas R
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.821.6
In many adults, regular aerobic exercise prevents development of vascular endothelial dysfunction with age as indicated by preserved endothelium‐dependent dilation (EDD). We hypothesized that suppression of endothelial signaling by the pro‐inflammatory transcription factor nuclear factor κB (NFκB) is a key mechanism involved. EDD was assessed by brachial artery flow‐mediated dilation (FMD) in young sedentary (YS, n=23) and middle‐aged and older sedentary (OS, n=23) and aerobic exercise‐trained (OT, n=23) healthy adults. OT had a greater FMD than OS (7.3±0.4% vs. 4.3±0.5%, P<0.05) and values not different from YS (6.9±0.6%). Endothelial cell expression of NFκB p65 was lower in OT and YS vs. OS (0.41±0.03 and 0.33±0.02 vs. 0.53±0.06, P<0.05). Short‐term treatment with salsalate, an inhibitor of NFκB, reduced endothelial cell NFκB p65 expression by 24% and improved FMD by 74% in OS (n=15, P<0.05), but had no effect in OT (n=13). Antioxidant (vitamin C) infusion improved FMD by 32% during placebo in OS (P<0.001), but had no effect during placebo in OT or during salsalate treatment in either group. Salsalate treatment reduced endothelial nitrotyrosine, a marker of oxidative stress, by 18% and NADPH oxidase p47 by 30% in OS (P<0.05), but did not affect OT. Reduced NFκB signaling and associated oxidative stress is an important mechanism by which aerobic exercise prevents vascular endothelial dysfunction with aging.