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Replicative senescence may be a suitable model for assessing in vivo endothelial cell oxidative stress and inflammation with aging in humans
Author(s) -
Rippe Catarina,
Blimline Mark,
Nelson Keri,
Seals Douglas R
Publication year - 2010
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.24.1_supplement.598.5
Subject(s) - in vivo , oxidative stress , superoxide dismutase , senescence , endothelium , inflammation , endothelial dysfunction , nitrotyrosine , in vitro , biology , endocrinology , chemistry , medicine , immunology , biochemistry , nitric oxide synthase , nitric oxide , microbiology and biotechnology
Oxidative stress and inflammation develop in the vascular endothelium with aging in rodents and humans and cause dysfunction. In vitro culture of endothelial cells to senescence may be a useful model of endothelial aging in humans, but this has not been established. Human aortic endothelial cells (HAEC) were analyzed by western blotting at early (passage 7–10) and senescent (passage 22–24) stages and compared with endothelial cells obtained in vivo from antecubital veins of healthy young (18–35 yr, n=26) and older (55–71 yr, n=26) adult males and analyzed using quantitative immunofluorescent staining. Nitrotyrosine, a marker of oxidative stress, was increased (P<0.05) with age both in vivo (1.6±0.2‐fold) and in vitro (1.9±0.1‐fold). The oxidant enzyme NADPH oxidase increased with age in vivo (1.6±0.1‐fold, P<0.05) and tended to increase in vitro (1.5±0.1‐fold, P=0.14). The antioxidant enzymes catalase and copper zinc superoxide dismutase (SOD) did not differ with age either in vivo or in vitro , whereas manganese SOD was selectively increased in senescent HAECs (1.6‐fold, P<0.05). The inflammatory proteins tumor necrosis factor α, nuclear factor κ B and monocyte chemoattractant protein‐1 increased (all P<0.05) with age both in vivo (1.6±0.2‐, 1.6±0.2‐, 1.4±0.2‐fold) and in vitro (2.4±0.5‐, 1.7±0.3‐, 1.6±0.1‐fold). In vitro culture of vascular EC to senescence may be a useful model of in vivo EC aging in humans for assessing oxidative stress and protein expression of oxidant and antioxidant enzymes and inflammatory molecules. NIH AG013038 and the Swedish Medical Research Council