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Reduced Endothelium‐Dependent Dilation with Aging in Humans is Associated with Endothelial Oxidative Stress and Enhanced Expression of NADPH Oxidase
Author(s) -
Donato Anthony J,
Levy Adam,
Eskurza Iratxe,
Pierce Gary L,
Silver Annemarie E,
Seals Douglas R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1372-d
Subject(s) - oxidative stress , xanthine oxidase , nadph oxidase , endothelium , medicine , nitrotyrosine , endocrinology , endothelial dysfunction , superoxide dismutase , chemistry , nitric oxide , enzyme , biochemistry , nitric oxide synthase
In rodents, reductions in endothelium‐dependent dilation (EDD) with aging are associated with the development of vascular oxidative stress. It is unknown if oxidative stress develops with aging in the vascular endothelium of humans and if it is related to reductions in EDD. To determine this, young (Y: 24 ± 1 yr; n = 41) and older (O: 63 ± 1 yr; n = 45) healthy sedentary men were studied. EDD (brachial artery flow‐mediated dilation, FMD) was 46% lower in the older vs. young men (4.3 ± 0.3 vs. 8.0 ± 0.3%, P < 0.01). Endothelial nitrotyrosine (NT) protein expression (quantitative immunofluorescence) was higher in arterial (1.20 ± 0.13 vs. 0.39 ± 0.04 NT intensity/HUVEC intensity, P < 0.01) and venous (0.55 ± 0.07 vs. 0.34 ± 0.03, P < 0.05) endothelial cells (EC) of the older vs. young men. NADPH oxidase p47 phox EC protein expression was higher in older subjects (0.67 ± 0.05 vs. 0.56 ± 0.05 NADPH oxidase p47 phox intensity/HUVEC intensity, P < 0.05), whereas xanthine oxidase was not different. EC cytosolic and mitochondrial superoxide dismutase expression did not differ. In the overall group, FMD was inversely related to NT expression in arterial EC (r = − 0.63, P < 0.01). These results indicate that oxidative stress develops in the vascular endothelium with aging in healthy sedentary men and is related to reductions in EDD. Increased expression of NADPH oxidase may contribute to endothelial oxidative stress with aging in humans. Supported by NIH AG013038 , AG006537 , AG022241 , RR00051, and AG00279