Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages.
Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte-macrophages.
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DOI：
10.1016/s0021-9258(19)50640-8
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
Margaret E. HaberlandSB;Gunther M. Flessll;Angelo M. Scanullll;A. Fogelman
中科院分区：
文献类型：
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作者：
Margaret E. HaberlandSB;Gunther M. Flessll;Angelo M. Scanullll;A. Fogelman
血浆中含apoB-100的脂蛋白（a）（Lp（a））水平升高与动脉粥样硬化和心肌梗死风险增加相关，但脂蛋白（a）加速这些过程的机制仍不清楚。在这项研究中，我们研究了载脂蛋白（a）与低密度脂蛋白（LDL）样Lp（a）颗粒的关联对脂蛋白经丙二醛或过渡金属诱导氧化修饰后受体识别特异性的影响。我们已经确定放射性碘标记Lp（a）的两种载脂蛋白组分，丙二醛修饰产生与天然Lp（a）在斯托克斯半径上相当的阴离子脂蛋白，并且N，N '-二取代的1-氨基-3-亚氨基丙烯衍生物优先将载脂蛋白（a）交联至apoB-100蛋白。与LDL一样，天然Lp（a）在人单核细胞-巨噬细胞中被LDL受体识别。与LDL一样，通过丙二醛对Lp（a）进行性修饰，可消除LDL受体对脂蛋白的识别，并通过人单核细胞-巨噬细胞的清道夫受体产生摄取和水解。我们认为动脉粥样硬化反应的细胞外成分对Lp（a）的内膜滞留使脂蛋白处于有利于随后过氧化修饰的微环境中。脂质过氧化物修饰的Lp（a）的慢性产生以及清道夫受体的未减轻的细胞清除可能有助于脂蛋白衍生的脂质在动脉粥样硬化反应的巨噬细胞衍生的泡沫细胞中的蓄积。
Increased plasma levels of the apoB-100-containing lipoprotein(a) (Lp(a)) are associated with an increased risk for atherosclerosis and myocardial infarction, but the mechanisms by which lipoprotein(a) may accelerate these processes remain obscure. In this study we have investigated the impact of the association of apoprotein(a) with the low density lipoprotein (LDL)-like Lp(a) particle upon specificity of receptor recognition after lipoprotein modification by malondialdehyde or transition metal-induced oxidation. We have determined that radioiodination labels both apoprotein components of Lp(a), that malondialdehyde modification produces an anionic lipoprotein comparable to native Lp(a) in Stokes' radius, and that N,N'-disubstituted 1-amino-3-iminopropene derivatives preferentially cross-link apoprotein(a) to apoB-100 protein. Like LDL, native Lp(a) is recognized in human monocyte-macrophages by the LDL receptor. Like LDL, progressive modification of Lp(a) by malondialdehyde abolishes lipoprotein recognition by the LDL receptor and produces uptake and hydrolysis by the scavenger receptor of human monocyte-macrophages. We propose that intimal retention of Lp(a) by extracellular components of the atherosclerotic reaction places the lipoprotein in a microenvironment favoring subsequent peroxidative modification. The chronic production of lipid peroxide-modified Lp(a) together with unmitigated cellular clearance by scavenger receptors may contribute to the accumulation of lipoprotein-derived lipid in macrophage-derived foam cells of the atherosclerotic reaction.