| Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint. | |
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MedLine Citation:
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PMID: 19706618 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Monika Biniecka; Aisling Kennedy; Ursula Fearon; Chin Teck Ng; Douglas J Veale; Jacintha N O'Sullivan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-08-24 |
Journal Detail:
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Title: Annals of the rheumatic diseases Volume: 69 ISSN: 1468-2060 ISO Abbreviation: Ann. Rheum. Dis. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-25 Completed Date: 2010-07-16 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372355 Medline TA: Ann Rheum Dis Country: England |
Other Details:
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Languages: eng Pagination: 1172-8 Citation Subset: IM |
Affiliation:
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Department of Rheumatology, Dublin Academic Health Care, St Vincent's University Hospital and The Conway Institute of Biomolecular and Biomedical Research, Dublin, Ireland. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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0/Angiogenesis Inducing Agents; 0/Biological Markers; 7782-44-7/Oxygen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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