Aging is associated with greater nuclear NFκB, reduced IκBα, and increased expression of proinflammatory cytokines in vascular endothelial cells of healthy humans
Open accessAbstract
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.
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Chronic low-grade inflammation develops in arteries with aging.
“Chronic low-grade inflammation develops in arteries with aging (44, 180)”
From Inorganic nitrite supplementation for healthy arterial aging (2014) · cites this paper as [44]
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- Authors
- Donato, A. J., Black, A. D., Jablonski, K. L., Gano, L. B., & Seals, D. R.
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Donato, Anthony J.
- Venue
- Aging Cell
- Publisher
- Wiley
- Published
- 2008-11-24
- Volume
- 7
- Issue
- 6
- Pages
- 805-812
- ISSN
- 1474-9718 (ISSN-L)
- 1474-9726
- PMC
- PMC3032405
- OpenAlex
- W2085355921
- Cited by
- 237
- References
- 41
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 3 · 2023: 12 · 2022: 10 · 2021: 22 · 2020: 12 · 2019: 15 · 2018: 12 · 2017: 9 · 2016: 18 · 2015: 15 · 2014: 19 · 2013: 16 · 2012: 15
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Aging Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (AG022241, K01AG029337, AG-006537, AG 029337, R01AG022241, R37AG013038, R01AG013038, R01AG006537, AG-013038)
- National Center for Research Resources (RR-00051, M01RR000051)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- aging, vascular endothelial cells, NF-κB p65, IκBα, inflammatory cytokines, interleukin-6, TNF-α, MCP-1, C-reactive protein, oxidized LDL, IκB kinase, peripheral veins, healthy older adults
- MeSH terms
- NF-KappaB Inhibitor alpha, Adult, Aged, Aging, Cell Nucleus, Female, Humans, Male, Middle Aged, Cytokines, NF-kappa B, Inflammation Mediators, I-kappa B Proteins, Endothelial Cells, Young Adult
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