Document Detail


Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.
MedLine Citation:
PMID:  19706618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: To assess levels of oxidative DNA damage (8-oxo-7,8-dihydro-2'-deoxyguanine; 8-oxo-dG) and lipid peroxidation (4-hydroxy-2-nonenal; 4-HNE) in serum, synovial fluid and tissue of patients with inflammatory arthritis in relation to in vivo hypoxia levels, disease activity and angiogenic markers. METHODS: Oxygen levels in synovial tissue were assessed using an oxygen/temperature probe. Nuclear and cytoplasmic 8-oxo-dG and 4-HNE levels were assessed in synovial tissue from 23 patients by immunohistochemistry. 8-Oxo-dG and 4-HNE levels in serum and synovial fluid were determined using 8-oxo-dG and hexanoyl-Lys (HEL) adduct ELISAs, respectively. Serum vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang2) levels were also measured by ELISA. RESULTS: The median oxygen tension in synovial tissue was profoundly hypoxic at 19.35 mm Hg (2.5%). Nuclear 8-oxo-dG levels were significantly higher than nuclear 4-HNE levels in the lining and sublining layers (all p<0.001). In contrast, cytoplasmic 4-HNE levels were higher than cytoplasmic 8-oxo-dG levels in both cell layers (all p<0.001). Reduced in vivo oxygen tension correlated with high lipid peroxidation in synovial fluid (p=0.027; r=0.54) and tissue (p=0.004; r=0.58). Serum VEGF levels were positively correlated with cytoplasmic 4-HNE expression (p=0.05; r=0.43) and intensity (p=0.006; r=0.59) in the lining layer. Serum Ang2 levels were positively correlated with nuclear 4-HNE expression and intensity in both cell layers (all p < or = 0.05). DAS28-C-reactive protein was correlated with nuclear 4-HNE expression in the sublining layer (p=0.02; r=0.48) and DAS28-erythrocyte sedimentation rate was correlated with nuclear 4-HNE expression in both cell layers (p < or = 0.03). CONCLUSIONS: Lipid peroxidation is associated with low oxygen tension in vivo, disease activity and angiogenic marker expression in inflammatory arthritis.
Authors:
Monika Biniecka; Aisling Kennedy; Ursula Fearon; Chin Teck Ng; Douglas J Veale; Jacintha N O'Sullivan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-24
Journal Detail:
Title:  Annals of the rheumatic diseases     Volume:  69     ISSN:  1468-2060     ISO Abbreviation:  Ann. Rheum. Dis.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-07-16     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372355     Medline TA:  Ann Rheum Dis     Country:  England    
Other Details:
Languages:  eng     Pagination:  1172-8     Citation Subset:  IM    
Affiliation:
Department of Rheumatology, Dublin Academic Health Care, St Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Angiogenesis Inducing Agents / metabolism
Arthritis / blood,  genetics,  metabolism*
Arthroscopy
Biological Markers / metabolism
Blood Sedimentation
Cell Hypoxia / physiology
DNA Damage
Female
Humans
Lipid Peroxidation / physiology
Male
Middle Aged
Oxidative Stress / physiology*
Oxygen / blood
Synovial Fluid / metabolism
Synovial Membrane / metabolism*
Chemical
Reg. No./Substance:
0/Angiogenesis Inducing Agents; 0/Biological Markers; 7782-44-7/Oxygen

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