Low density lipoprotein of synovial fluid in inflammatory joint disease ismildly oxidized

Oxidatively modified low density lipoprotein (LDL) has many biological acti vities which could contribute to the pathology of the atherosclerotic lesio n. Because atherosclerosis has an inflammatory component, there has been mu ch interest in the extent to which LDL could be oxidatively modified in viv o by inflammation. The present study examined LDL present in an accessible inflammatory site, the inflamed synovial joint, for evidence of composition al change and oxidative modification. LDL was isolated from knee joint syno vial fluid (SF) from subjects with inflammatory arthropathies and also from marched plasma samples. SF and plasma LDL had similar free cholesterol and alpha-tocopherol content, but SF LDL had a lower content of esterified cho lesterol. 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 detecte d in any samples, but cholesterol ester hydroperoxide levels were greater i n SF than in plasma LDL. When samples from three subjects were incubated wi th macrophages, the SF LDL did not cause significant loading of the cells w ith cholesterol or cholesterol esters, in contrast to the situation with ac etylated LDL. Overall, the SF LDL displayed evidence of slightly increased oxidation by comparison with matched plasma samples. Despite their isolatio n from an environment with active inflammation, changes were modest compare d with those resulting from Cu2+ treatment. Thus, extensive LDL oxidation i s not a necessary correlate of location in a chronic inflammatory site, eve n though it is characteristic of atherosclerotic lesions.