Objectives: To assess levels of oxidative DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in serum, synovial fluid and tissue of inflammatory arthritis patients 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 were assessed in synovial tissue from 23 patients using immunohistochemistry. 8-oxo-dG and 4-HNE levels in serum and synovial fluid were determined using 8-oxo-dG and Hexanoyl-Lys (HEL) adduct ELISA’s respectively. Serum VEGF and Ang2 were also measured by ELISA.
Results: The median pO2 level in synovial tissue was profoundly hypoxic at 19.35mmHg (2.5%). Nuclear 8-oxo-dG was significantly higher than nuclear 4-HNE levels in lining and sublining layers (all p values<0.001). In contrast, cytoplasmic 4-HNE levels were higher than cytoplasmic 8-oxo-dG in both cell layers (all p values <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 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 positively correlated with nuclear 4-HNE expression and intensity in both cell layers (all p values<0.05). DAS28-CRP correlated with nuclear 4-HNE expression in sublining layer (p=0.02; r=0.48) and DAS28-ESR correlated with nuclear 4-HNE expression in both cell layers (p values<0.03).
Conclusions: Lipid peroxidation is associated with low oxygen tension in vivo, with disease activity and angiogenic marker expression in inflammatory arthritis.