Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.

Hdl Handle:
http://hdl.handle.net/10147/207693
Title:
Oxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.
Authors:
Biniecka, Monika; Kennedy, Aisling; Fearon, Ursula; Ng, Chin Teck; Veale, Douglas J; O'Sullivan, Jacintha N
Affiliation:
Department of Rheumatology, Dublin Academic Health Care, St Vincent's University , Hospital and The Conway Institute of Biomolecular and Biomedical Research,, Dublin, Ireland.
Citation:
Ann Rheum Dis. 2010 Jun;69(6):1172-8. Epub 2009 Aug 24.
Journal:
Annals of the rheumatic diseases
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207693
DOI:
10.1136/ard.2009.111211
PubMed ID:
19706618
Abstract:
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.
Language:
eng
MeSH:
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
ISSN:
1468-2060 (Electronic); 0003-4967 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorBiniecka, Monikaen_GB
dc.contributor.authorKennedy, Aislingen_GB
dc.contributor.authorFearon, Ursulaen_GB
dc.contributor.authorNg, Chin Tecken_GB
dc.contributor.authorVeale, Douglas Jen_GB
dc.contributor.authorO'Sullivan, Jacintha Nen_GB
dc.date.accessioned2012-02-01T10:35:08Z-
dc.date.available2012-02-01T10:35:08Z-
dc.date.issued2012-02-01T10:35:08Z-
dc.identifier.citationAnn Rheum Dis. 2010 Jun;69(6):1172-8. Epub 2009 Aug 24.en_GB
dc.identifier.issn1468-2060 (Electronic)en_GB
dc.identifier.issn0003-4967 (Linking)en_GB
dc.identifier.pmid19706618en_GB
dc.identifier.doi10.1136/ard.2009.111211en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207693-
dc.description.abstractOBJECTIVES: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshAngiogenesis Inducing Agents/metabolismen_GB
dc.subject.meshArthritis/blood/genetics/*metabolismen_GB
dc.subject.meshArthroscopyen_GB
dc.subject.meshBiological Markers/metabolismen_GB
dc.subject.meshBlood Sedimentationen_GB
dc.subject.meshCell Hypoxia/physiologyen_GB
dc.subject.meshDNA Damageen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshHumansen_GB
dc.subject.meshLipid Peroxidation/physiologyen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshOxidative Stress/*physiologyen_GB
dc.subject.meshOxygen/blooden_GB
dc.subject.meshSynovial Fluid/metabolismen_GB
dc.subject.meshSynovial Membrane/*metabolismen_GB
dc.titleOxidative damage in synovial tissue is associated with in vivo hypoxic status in the arthritic joint.en_GB
dc.contributor.departmentDepartment of Rheumatology, Dublin Academic Health Care, St Vincent's University , Hospital and The Conway Institute of Biomolecular and Biomedical Research,, Dublin, Ireland.en_GB
dc.identifier.journalAnnals of the rheumatic diseasesen_GB
dc.description.provinceLeinster-

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