Document Detail


Pressure-induced cellular senescence: a mechanism linking venous hypertension to venous ulcers.
MedLine Citation:
PMID:  15734488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
INTRODUCTION: 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). MATERIALS AND METHODS: 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. RESULTS: NNF cultured at ATM + 60 mmHg and ATM + 120 mmHg showed increased SA-beta-Gal activity (P <0.05), and reduced growth rates (P <0.05) at 11 days. These effects were not seen at ATM + 30 mmHg. NNF grown with TGF-beta did not show augmented SA-beta-Gal staining. CONCLUSIONS: Pressure-exposed NNF demonstrated an accelerated aging phenomenon similar to fibroblasts isolated from venous ulcers. This aging effect was directly related to the level of pressure. TGF-beta did not augment the aging effect. This study suggests that pressure elevations result in altered cell function and accelerated aging that may contribute to the slowed healing seen in patients with venous insufficiency.
Authors:
Andrew C Stanley; Nathanial N Fernandez; Karen M Lounsbury; Kim Corrow; Turner Osler; Christopher Healey; Patrick Forgione; Steven R Shackford; Michael A Ricci
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of surgical research     Volume:  124     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-28     Completed Date:  2005-04-12     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  112-7     Citation Subset:  IM    
Affiliation:
The Division of Vascular Surgery, University of Vermont College of Medicine, Burlington, Vermont 05405-0680, USA. andrew.stanley@uvm.edu
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MeSH Terms
Descriptor/Qualifier:
Cell Aging / physiology*
Cell Culture Techniques
Cell Proliferation
Fibroblasts / immunology,  physiology*
Humans
Infant, Newborn
Pressure / adverse effects*
Skin
Transforming Growth Factor beta / adverse effects,  immunology
Varicose Ulcer / etiology,  immunology,  physiopathology*
Venous Pressure / physiology*
beta-Galactosidase / analysis
Chemical
Reg. No./Substance:
0/Transforming Growth Factor beta; EC 3.2.1.23/beta-Galactosidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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