Abstract 649: Effect of Aging and Habitual Endurance Exercise on Vascular Endothelial NF-kappa;B Protein Expression and Dilation in Humans
Background: Aging is a major risk factor for clinical atherosclerotic diseases and is associated with impaired vascular endothelial function (e.g., decreased endothelium-dependent dilation, EDD) and reduced exercise capacity. Middle-aged and older adults who habitually perform aerobic exercise have a reduced risk of atherosclerotic diseases, preserved EDD and enhanced exercise capacity. The molecular mechanisms for these divergent effects are incompletely understood, but may involve different chronic states of low-grade vascular oxidative stress and inflammation. Nuclear factor-kappa B (NF-κB) is key redox-sensitive pro-inflammatory transcription factor linked to atherosclerosis. We hypothesized that these respective functional phenotypes of sedentary and physically active aging would be associated with increased and reduced endothelial NF-κB expression, respectively.
Methods: EDD (brachial artery flow- mediated dilation), maximal exercise capacity (maximal oxygen uptake, VO2 max) and venous endothelial cell protein expression of NF-κB p65 subunit (quantitative immunofluorescence of protein normalized to HUVEC control) were determined in young sedentary (YS: n=41, age 23 ± 1 yrs, 35M), older sedentary (OS: n=48, age 63 ± 1 yrs, 35M), and older trained (OT: n=22, age 63 ± 1 yrs, 22M) healthy adults.
Results: There was decline in EDD (OS: 0.17 ± 0.01 mm, 4.35 ± 0.33 %; YS: 0.30 ± 0.01 mm, 7.52 ± 0.33 %, p<0.01; OT: 0.25 ± 0.01 mm, 6.32 ± 0.39 %, p<0.01) and VO2 max (OS: 27.9 ± 0.7; YS: 44.7 ± 1.0, p<0.001; OT: 39.6 ± 0.8 ml/kg/min, p<0.001) in OS compared with YS, but not to OT. Endothelial NF-κB protein expression was greater in OS compared with YS, but was attenuated in OT (OS: 0.64 ± 0.06; YS: 0.37 ± 0.04, p<0.001; OT: 0.44 ± 0.05, p=0.02). In a pooled group, NF-κB was inversely related to EDD (n=22; r=−0.427, p<0.05) and VO2 max (n=45; r =−0.365, p<0.05).
Conclusions: Vascular endothelial expression of NF-κB is increased in sedentary, but not in habitually exercising middle-aged and older healthy adults. These differences in endothelial NF-κB expression may be an important molecular mechanism contributing to differences in endothelial function, exercise capacity and risk of atherosclerotic diseases with sedentary and physically active aging in humans.