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Keywords:

  • endothelium-dependent dilation;
  • IL-6;
  • TNF-α;
  • MCP-1;
  • RAGE;
  • COX-2

Summary

The vascular endothelium may develop a proinflammatory profile with aging, but evidence is limited in humans. Expression of inflammatory proteins was determined in vascular endothelial cells (EC) obtained from peripheral veins of 24 young (23 ± 1 years, mean ± SE) and 36 older (63 ± 1) healthy men and women using quantitative immunofluorescence. The older subjects had lower vascular endothelium-dependent dilation (forearm blood flow responses to acetylcholine, p < 0.05), and higher plasma concentrations of C-reactive protein, interleukin-6 (IL-6), and oxidized low-density lipoprotein (all p < 0.05), but not tumor necrosis factor-α (TNF-α). Total (O: 0.52 ± 0.04 vs. Y: 0.33 ± 0.05 NFκB/HUVEC intensity, p < 0.05) and nuclear (O: 0.59 ± 0.04 vs. Y: 0.41 ± 0.04) expression of nuclear factor κ B p65 (NFκB), a proinflammatory gene transcription factor, was greater in EC from the older subjects (p < 0.05). EC expression of the inhibitor (of nuclear translocation) of NFκB (IκBα) was lower in the older subjects (O: 0.16 ± 0.02 vs. Y: 0.24 ± 0.03, p < 0.05), whereas IκB kinase (IκK) was not different. EC expression of the proinflammatory proteins IL-6 (O: 0.42 ± 0.06 vs. Y: 0.29 ± 0.03, p < 0.05), TNF-α (O: 0.52 ± 0.06 vs. Y: 0.33 ± 0.05, p < 0.05) and monocyte chemoattractant protein 1 (MCP-1) (O: 0.59 ± 0.06 vs. Y: 0.38 ± 0.02, p < 0.05) was greater in the older subjects, whereas cyclooxygenase 2 and the receptor for advanced glycation end-products did not differ. These findings indicate that impaired function with aging in healthy adults is associated with the development of a proinflammatory phenotype in the vascular endothelium that could be caused in part by reduced IκB-mediated inhibition of NFκB.