A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma
A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma
复制标题
DOI：
10.1194/jlr.m800174-jlr200
复制
发表时间：
2008-10-01
影响因子：
6.5
通讯作者：
Tsimikas, Sotirios
中科院分区：
文献类型：
--
作者：
Bergmark, Claes;Dewan, Asheesh;Tsimikas, Sotirios
载脂蛋白B-100 （apoB-100）颗粒上的氧化磷脂（OxPLs）与脂蛋白[a] （Lp[a]）密切相关。在本研究中，我们评估了Lp[a]在人血浆中是否优先成为OxPL的载体。用单克隆抗体E06测定apoB-100颗粒上OxPL的含量，该抗体识别氧化而非天然磷脂的磷酸胆碱（PC）头群。为了评估OxPLs是否优先与Lp[a]结合，而不是其他脂蛋白，进行了免疫沉淀和超离心实验、体外转移研究和化学发光elisa。用载脂蛋白[a]（载脂蛋白[a]）特异性抗体从人血浆中免疫沉淀Lp[a]表明，85%以上的E06反应性（即OxPL）与Lp[a]共免疫沉淀。超离心实验表明，与其他载脂蛋白相反，几乎所有的OxPLs都存在于含有载脂蛋白[a]的组分中。体外转移研究表明，即使在水相缓冲液中，氧化LDL也以时间和温度依赖的方式优先将OxPLs提供给Lp[a]，而不是LDL。将血浆暴露于各种脂质溶剂后，可从分离的Lp中提取约50%的E06免疫反应性[a]。这些数据表明，Lp[a]是人血浆中含pc的OxPL的优先载体。Lp[a]的这一独特特性为其生理功能和动脉粥样硬化机制提供了新的见解。
Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] as opposed to other lipoproteins, immuno-precipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apo[a], as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lp[a], as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents. These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.