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

作者：Donato Anthony J^*; Black Alexander D; Jablonski Kristen L; Gano Lindsey B; Seals Douglas R

来源：AGING CELL, 2008, 7(6): 805-812.

DOI：10.1111/j.1474-9726.2008.00438.x

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

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 NF kappa B/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 (NF kappa B), 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 NF kappa B (I kappa B alpha) was lower in the older subjects (O: 0.16 +/- 0.02 vs. Y: 0.24 +/- 0.03, p < 0.05), whereas I kappa B kinase (I kappa K) 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 I kappa B-mediated inhibition of NF kappa B.

• 出版日期2008-12