The oxidized phospholipids linked to human apolipoprotein(a) do not derive from circulating low-density lipoproteins and are probably of cellular origin
The oxidized phospholipids linked to human apolipoprotein(a) do not derive from circulating low-density lipoproteins and are probably of cellular origin
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DOI：
10.1096/fj.08-122002
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发表时间：
2009-03-01
期刊：
影响因子：
4.8
通讯作者：
Scanu, Angelo M.
中科院分区：
文献类型：
--
作者：
Edelstein, Celina;Philips, Binu;Scanu, Angelo M.
脂蛋白（a）[Lp（a）]是一种心血管风险因子，是一种低密度脂蛋白（LDL）变体，可与氧化磷脂（oxPL）结合;然而，其结合模式和来源尚未明确。我们从高Lp（a）受试者的血浆中分离LDL和Lp（a），并在每个Lp（a）颗粒中将载脂蛋白（a）[apo（a）]与LDL组分Lp（a（-））分离。使用对oxPL具有已知特异性的单克隆抗体T15通过ELISA测定这些产物。在每例受试者中，T15反应性仅限于apo（a）。此外，与apo（a）结合的oxPL量不受血浆Lp（a）水平和apo（a）大小多态性的影响。我们先前已经证明kringle V（KV）是人apo（a）中oxPL连接的位点。在这项工作中，我们在人胚肾细胞中表达了一种含有KV的重组体，当从培养基中纯化时，含有oxPL。总之，在人血浆Lp（a）中，oxPL位于apo（a）中，而不是循环LDL中，表明其来源于细胞。后一种概念得到了表达的含KV的apo（a）微结构域显示oxPL反应性的研究的支持。因此，apo（a）可以在能够产生oxPL的细胞环境中经历潜在的致病性翻译后修饰。埃德尔斯坦，C.，Philips，B.，Pfaffinger，D.，Scanu，A. M.与人载脂蛋白（a）连接的氧化磷脂不是来自循环低密度脂蛋白，可能是细胞来源。FASEB J. 23，950-956（2009）
Lipoprotein (a) [Lp(a)], a cardiovascular risk factor, is a low-density lipoprotein (LDL) variant shown to bind to oxidized phospholipids (oxPLs); however, its binding mode and origin have not been clearly established. We isolated both LDL and Lp(a) from the plasma of a population of high-Lp(a) subjects and in each Lp(a) particle separated apolipoprotein(a) [apo(a)], from the LDL component, Lp(a(-)). These products were assayed by an ELISA using monoclonal antibody T15 with a known specificity for oxPLs. In each subject, the T15 reactivity was confined to apo(a). Moreover, the amount of oxPL bound to apo(a) was unaffected by plasma Lp(a) levels and apo(a) size polymorphism. We have previously shown that kringle V (KV) is the site of oxPL linkage in human apo(a). In this work, we expressed in human embryonic kidney cells a KV-containing recombinant that, when purified from the medium, contained oxPLs. In summary, in human plasma Lp(a), the oxPLs are located in apo(a) and not in the circulating LDLs, suggesting a cellular origin. This latter concept is supported by the studies in which an expressed KV-containing apo(a) microdomain exhibited oxPL reactivity. Thus, apo(a) can undergo potentially pathogenic posttranslational modifications in a cellular environment able to generate oxPL.-Edelstein, C., Philips, B., Pfaffinger, D., Scanu, A. M. The oxidized phospholipids linked to human apolipoprotein(a) do not derive from circulating low-density lipoproteins and are probably of cellular origin. FASEB J. 23, 950-956 (2009)