Pressure-induced cellular senescence: a mechanism linking venous hypertension to venous ulcers

Slow healing of ulcers in chronic venous insufficiency (CVI) has long been thought secondary to venous hypertension. Dermal fibroblasts isolated from venous ulcers have morphologies and protein production suggestive of premature aging. In this study, we hypothesized that neonatal fibroblasts (NNF) c...

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Published in:The Journal of surgical research 2005-03, Vol.124 (1), p.112-117
Main Authors: Stanley, Andrew C, Fernandez, Nathanial N, Lounsbury, Karen M, Corrow, Kim, Osler, Turner, Healey, Christopher, Forgione, Patrick, Shackford, Steven R, Ricci, Michael A
Format: Article
Language:English
Subjects:
beta-Galactosidase - analysis
Cell Culture Techniques
Cell Proliferation
Cellular Senescence - physiology
Fibroblasts - immunology
Fibroblasts - physiology
Humans
Infant, Newborn
Pressure - adverse effects
Skin
Transforming Growth Factor beta - adverse effects
Transforming Growth Factor beta - immunology
Varicose Ulcer - etiology
Varicose Ulcer - immunology
Varicose Ulcer - physiopathology
Venous Pressure - physiology
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Summary:Slow healing of ulcers in chronic venous insufficiency (CVI) has long been thought secondary to venous hypertension. Dermal fibroblasts isolated from venous ulcers have morphologies and protein production suggestive of premature aging. In this study, we hypothesized that neonatal fibroblasts (NNF) cultured under elevated pressure will demonstrate premature aging and that this effect will be augmented by an inflammatory mediator, transforming growth factor beta (TGF-beta). A unique pressure incubator was used to culture NNF at atmospheric pressure (ATM), ATM + 30 mmHg, ATM + 60 mmHg, and ATM +120 mmHg. Some pressure-exposed NNF were also cultured with TGF- beta (1 ng/ml). Growth rates were determined by flow cytometry. Senescent cells were identified by staining with a marker for cellular senescence, beta-galactosidase (SA-beta-Gal). Light microscopy and digital imaging were used to evaluate cell morphology. Paired linear models and comparison of the slopes were used for statistical analysis of growth. chi2 analysis was used to compare senescence rates. NNF cultured at ATM + 60 mmHg and ATM + 120 mmHg showed increased SA-beta-Gal activity (P
ISSN:0022-4804
DOI:10.1016/j.jss.2004.09.013