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.
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.
Donato
Anthony J
AJ
Department of Integrative Physiology, University of Colorado, Boulder, Colorado 80309, USA. tony.donato@colorado.edu
Black
Alexander D
AD
Jablonski
Kristen L
KL
Gano
Lindsey B
LB
Seals
Douglas R
DR
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
D016207:Cytokines; D020672:I-kappa B Proteins; D018836:Inflammation Mediators; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D000072000:NF-KappaB Inhibitor alpha
FASEB J. 2003 Jun;17(9):1183-5
12709402
Circulation. 2003 Nov 11;108(19):2317-22
14568895
Circ Res. 2002 Jun 14;90(11):1159-66
12065318
Antioxid Redox Signal. 2006 Mar-Apr;8(3-4):572-81
16677101
Circ Res. 2007 Jun 8;100(11):1659-66
17478731
J Gerontol A Biol Sci Med Sci. 2007 Apr;62(4):427-33
17452738
Circulation. 2005 Jul 5;112(1):25-31
15983251
J Appl Physiol (1985). 2002 Mar;92(3):1331-8
11842075
J Physiol. 2005 Nov 1;568(Pt 3):1057-65
16141271
Hypertension. 2004 Aug;44(2):134-9
15249547
Circulation. 2007 Aug 7;116(6):669-76
17664374
Circulation. 2000 Sep 19;102(12):1351-7
10993851
Herz. 2004 Dec;29(8):733-40
15599669
Hypertension. 2008 Jul;52(1):72-9
18504322
Hypertension. 2007 Jul;50(1):219-27
17452499
J Appl Physiol (1985). 2008 Oct;105(4):1359-63
18669935
J Physiol. 2006 Mar 15;571(Pt 3):661-8
16439428
Antioxid Redox Signal. 2001 Feb;3(1):147-56
11291593
Mech Ageing Dev. 2004 Feb;125(2):95-8
15037008
Arterioscler Thromb Vasc Biol. 2003 Feb 1;23(2):168-75
12588755
Exp Gerontol. 2004 Mar;39(3):407-13
15036400
Am J Physiol. 1995 Jun;268(6 Pt 2):H2288-93
7611479
Am J Physiol Heart Circ Physiol. 2006 Oct;291(4):H1694-9
16973825
Glycobiology. 2005 Jul;15(7):16R-28R
15764591
Circulation. 2002 Aug 6;106(6):640-2
12163419
Circ Res. 2007 Aug 3;101(3):227-9
17673681
J Appl Physiol (1985). 2002 Jun;92(6):2303-8
12015340
Circulation. 2007 Feb 6;115(5):627-37
17242275
Radiology. 1999 Sep;212(3):655-64
10478228
J Am Coll Cardiol. 2003 Oct 1;42(7):1149-60
14522472
Hypertension. 2005 Jun;45(6):1107-12
15867135
Am J Med. 1999 May;106(5):506-12
10335721
Arterioscler Thromb Vasc Biol. 2005 May;25(5):904-14
15731497
Circulation. 2003 Jan 7;107(1):139-46
12515756
J Vasc Surg. 2003 Aug;38(2):374-9
12891123
Circulation. 2002 Mar 5;105(9):1135-43
11877368
Circulation. 2000 Aug 29;102(9):1000-6
10961964
Physiol Genomics. 2004 Mar 12;17(1):21-30
15020720
J Gerontol A Biol Sci Med Sci. 2006 Mar;61(3):232-44
16567371
Physiol Genomics. 2008 Feb 19;32(3):409-18
18056786
J Biol Chem. 1999 Sep 24;274(39):27339-42
10488062