Nuclear factor κB‐associated inflammation mediates impaired vascular endothelial function in non‐diabetic middle‐aged and older overweight/obese men

Abstract

Healthy middle‐aged/older (MA/O) sedentary men demonstrate vascular endothelial dysfunction with increased endothelial expression of nuclear factor‐kappa B (NFκB), a key proinflammatory nuclear transcription factor. However, there is no direct evidence that NFκB‐associated vascular inflammation mediates endothelial dysfunction in MA/O adults. High doses of Salsalate (4500 mg/d; therapeutic [plasma] 22.2 ± 1.7 mg/100ml, mean ± SE), an aspirin‐like agent that inhibits NFκB, was ingested for 4 days (randomized, placebo‐controlled, double‐blind crossover design) by 10 non‐diabetic overweight or obese MA/O men (62 ± 2 y; BMI 31.4 ± 2 kg/m2) with low‐grade inflammation (plasma C‐reactive protein 2.0 ± 0.7 mg/L). Salsalate reduced total (−30%: 0.42 ± 0.07 vs. 0.60 ± 0.09 intensity/HUVEC intensity, P=0.03) and nuclear (−23%: 128 ± 25 vs. 167 ± 24 total intensity, P=0.06) expression of NFκB p65 in vascular endothelial cells (quantitative immunofluorescence), and increased endothelium‐dependent dilation (EDD, brachial artery flow‐mediated dilation) by 100% (6.2 ± 0.6 vs. 3.1 ± 0.6%, P<0.001) without affecting endothelium‐independent dilation (brachial artery dilation to sublingual nitroglycerin) (19.5 ± 2.2 vs. 19.3 ± 1.6%, P=0.80). These results support the idea that NFκB‐associated vascular inflammation mediates endothelial dysfunction in MA/O overweight/obese men. NIH AG006537, AG013038, AG022241