Low density lipoprotein of synovial fluid in inflammatory joint disease is mildly oxidized

Oxidatively modified low density lipoprotein (LDL) has many biological activities which could contribute to the pathology of the atherosclerotic lesion. Because atherosclerosis has an inflammatory component, there has been much interest in the extent to which LDL could be oxidatively modified in vivo by inflammation. The present study examined LDL present in an accessible inflammatory site, the inflamed synovial joint, for evidence of compositional change and oxidative modification. LDL was isolated from knee joint synovial fluid (SF) from subjects with inflammatory arthropathies and also from matched plasma samples. SF and plasma LDL had similar free cholesterol and α-tocopherol content, but SF LDL had a lower content of esterified cholesterol. On electrophoresis, SF LDL was slightly more electronegative than LDL from matched plasma samples, but the changes were much less than those resulting from Cu²⁺-treatment of LDL. Oxidized cholesterol was not detected in any samples, but cholesterol ester hydroperoxide levels were greater in SF than in plasma LDL. When samples from three subjects were incubated with macrophages, the SF LDL did not cause significant loading of the cells with cholesterol or cholesterol esters, in contrast to the situation with acetylated LDL. Overall, the SF LDL displayed evidence of slightly increased oxidation by comparison with matched plasma samples. Despite their isolation from an environment with active inflammation, changes were modest compared with those resulting from Cu²⁺ treatment. Thus, extensive LDL oxidation is not a necessary correlate of location in a chronic inflammatory site, even though it is characteristic of atherosclerotic lesions.