Ylä-Herttuala S, Palinski W, Rosenfeld M E, Steinberg D, Witztum J L
Department of Medicine, University of California, San Diego, La Jolla 92093-0613.
Eur Heart J. 1990 Aug;11 Suppl E:88-99. doi: 10.1093/eurheartj/11.suppl_e.88.
Each method used for the extraction and isolation of intimal lipoproteins has advantages and disadvantages. Gentle extraction methods are needed to characterize subtle modifications in the structure and biologic properties of the lipoproteins, whereas more aggressive methods are needed if the goal is to maximize the yield of lipoproteins from atherosclerotic arteries. The present paper evaluates different methods used for the isolation of intimal lipoproteins. Normal intima contains remnant-like and low density lipoprotein (LDL)-like particles that more strongly stimulate cholesterol esterification in macrophages than do control plasma LDL. Both fractions contain apolipoprotein (apo) E but neither shows clear signs of oxidative modification. LDL-like particles from atherosclerotic lesions, on the other hand, contain malondialdehyde- and 4-hydroxynonenal-lysine adducts in apo B, are chemotactic for monocytes and show increased degradation in macrophages, a process that oxidized LDL prepared in vitro can compete with. The findings support the conclusion that at least a portion of the LDL isolated from atherosclerotic lesions is similar, if not identical, to oxidatively modified LDL.
用于提取和分离内膜脂蛋白的每种方法都有其优缺点。要表征脂蛋白结构和生物学特性的细微变化,需要采用温和的提取方法;而如果目标是从动脉粥样硬化动脉中最大限度地提高脂蛋白产量,则需要更具侵略性的方法。本文评估了用于分离内膜脂蛋白的不同方法。正常内膜含有残留样和低密度脂蛋白(LDL)样颗粒,它们比对照血浆LDL更强烈地刺激巨噬细胞中的胆固醇酯化。这两个部分都含有载脂蛋白(apo)E,但均未显示出明显的氧化修饰迹象。另一方面,来自动脉粥样硬化病变的LDL样颗粒在载脂蛋白B中含有丙二醛和4-羟基壬烯醛-赖氨酸加合物,对单核细胞具有趋化作用,并在巨噬细胞中显示出增加的降解,这一过程体外制备的氧化LDL可以与之竞争。这些发现支持以下结论:从动脉粥样硬化病变中分离出的至少一部分LDL即使不与氧化修饰的LDL完全相同,也与之相似。