Aging is associated with greater nuclear NFκB, reduced IκBα, and increased expression of proinflammatory cytokines in vascular endothelial cells of healthy humans
Open Access
- 24 November 2008
- journal article
- research article
- Published by Wiley in Aging Cell
- Vol. 7 (6), 805-812
- https://doi.org/10.1111/j.1474-9726.2008.00438.x
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‐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.This publication has 42 references indexed in Scilit:
- Cytochrome P-450 2C9 signaling does not contribute to age-associated vascular endothelial dysfunction in humansJournal of Applied Physiology, 2008
- Weight Loss Alone Improves Conduit and Resistance Artery Endothelial Function in Young and Older Overweight/Obese AdultsHypertension, 2008
- Proinflammatory Profile Within the Grossly Normal Aged Human Aortic WallHypertension, 2007
- Resveratrol attenuates TNF-α-induced activation of coronary arterial endothelial cells: role of NF-κB inhibitionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- The Molecular Inflammatory Process in AgingAntioxidants and Redox Signaling, 2006
- Upregulation of Aortic Adhesion Molecules During AgingThe Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2006
- C-Reactive Protein and the 10-Year Incidence of Coronary Heart Disease in Older Men and WomenCirculation, 2005
- Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal WomenHypertension, 2005
- Local Shear Stress and Brachial Artery Flow-Mediated DilationHypertension, 2004
- Age associated changes of AGE-receptor expression: RAGE upregulation is associated with human heart dysfunctionExperimental Gerontology, 2004