title: Aging is associated with greater nuclear NF kappa B, reduced I kappa B alpha, and increased expression of proinflammatory cytokines in vascular endothelial cells of healthy humans.
abstract: 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-alpha (TNF-alpha). Total (O: 0.52 +/- 0.04 vs. Y: 0.33 +/- 0.05 NFkappaB/HUVEC intensity, p < 0.05) and nuclear (O: 0.59 +/- 0.04 vs. Y: 0.41 +/- 0.04) expression of nuclear factor kappa B p65 (NFkappaB), 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 NFkappaB (IkappaBalpha) was lower in the older subjects (O: 0.16 +/- 0.02 vs. Y: 0.24 +/- 0.03, p < 0.05), whereas IkappaB kinase (IkappaK) 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-alpha (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 IkappaB-mediated inhibition of NFkappaB.
authors.affiliation: Department of Integrative Physiology, University of Colorado, Boulder, Colorado 80309, USA. tony.donato@colorado.edu
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Black
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Jablonski
authors.forename: Lindsey B
authors.initials: LB
authors.lastname: Gano
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D055815:Young Adult
chemical_list: D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha
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