James M J, van Reyk D, Rye K A, Dean R T, Cleland L G, Barter P J, Jessup W
Rheumatology Unit, Royal Adelaide Hospital, SA, Australia.
Lipids. 1998 Nov;33(11):1115-21. doi: 10.1007/s11745-998-0313-8.
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 alpha-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.
氧化修饰的低密度脂蛋白（LDL）具有多种生物学活性，这些活性可能促成动脉粥样硬化病变的病理过程。由于动脉粥样硬化具有炎症成分，因此人们对LDL在体内被炎症氧化修饰的程度非常感兴趣。本研究检查了可及的炎症部位——发炎的滑膜关节中存在的LDL，以寻找其成分变化和氧化修饰的证据。从患有炎性关节病的受试者的膝关节滑液（SF）以及匹配的血浆样本中分离LDL。SF和血浆LDL的游离胆固醇和α-生育酚含量相似，但SF LDL的酯化胆固醇含量较低。电泳时，SF LDL比匹配血浆样本中的LDL略带负电，但变化远小于Cu2+处理LDL所导致的变化。在任何样本中均未检测到氧化胆固醇，但SF中胆固醇酯氢过氧化物水平高于血浆LDL。当将三名受试者的样本与巨噬细胞一起孵育时，与乙酰化LDL的情况相反，SF LDL不会导致细胞显著负载胆固醇或胆固醇酯。总体而言，与匹配的血浆样本相比，SF LDL显示出氧化略有增加的证据。尽管它们是从具有活跃炎症的环境中分离出来的，但与Cu2+处理所导致的变化相比，变化程度较小。因此，即使广泛的LDL氧化是动脉粥样硬化病变的特征，但它并非慢性炎症部位定位的必然相关因素。
