Chang M Y, Lees A M, Lees R S
Boston Heart Foundation, Cambridge, Massachusetts 02142.
Biochemistry. 1993 Aug 24;32(33):8518-24. doi: 10.1021/bi00084a018.
Chemically or enzymatically modified low-density lipoproteins (LDL), with and without changes in surface charge, were studied in vivo in the healing, balloon catheter-deendothelialized rabbit aorta to determine the effect of LDL modification on its accumulation in arterial lesions. In this model, in which healing (reendothelialization) proceeds radially outward from individual aortic branch arteries, it was previously shown by autoradiography that two kinetically distinct compartments accumulated 125I-labeled LDL. In aortic regions which were still deendothelialized, accumulation was diffuse and labile. In contrast, at the edges of the islands of regenerating endothelium, LDL accumulation was intensely focal, as it is in human atherosclerotic lesions, and persisted for at least 40 h after injection in spite of falling levels of radiolabeled LDL in plasma [Chang, M. Y., et al. (1992) Arterioscler. Thromb. 12, 1088-1098]. In the present study, modified LDLs with gradations in charge change were prepared to clarify the role of changes in surface charge on focal aortic LDL accumulation. Oxidized LDL (weakly anionized), desialated LDL (weakly cationized), and reductively methylated LDL (no change in net charge) all accumulated focally. Focal accumulation of native LDL also occurred in ballooned rabbits fed probucol to inhibit LDL oxidation. Strongly anionized succinylated and diazobenzenearsonylated LDL and strongly cationized dimethylpropanediamine LDL did not accumulate focally. The results support the concept that focal sequestration of LDL in arterial lesions is mediated by specific, oxidation-independent patterns of charge and polarity on LDL which are disrupted by major changes in LDL surface charge.
研究了化学或酶修饰的低密度脂蛋白（LDL），其表面电荷有或无变化，在愈合的、经球囊导管去内皮的兔主动脉中进行体内研究，以确定LDL修饰对其在动脉病变中蓄积的影响。在这个模型中，愈合（再内皮化）从各个主动脉分支动脉径向向外进行，先前通过放射自显影显示，两个动力学上不同的区室蓄积了125I标记的LDL。在仍处于去内皮状态的主动脉区域，蓄积是弥散且不稳定的。相反，在再生内皮岛的边缘，LDL蓄积强烈聚焦，就像在人类动脉粥样硬化病变中一样，并且在注射后至少持续40小时，尽管血浆中放射性标记的LDL水平下降[Chang, M. Y., 等人（1992年）《动脉硬化血栓形成》12, 1088 - 1098]。在本研究中，制备了具有电荷变化梯度的修饰LDL，以阐明表面电荷变化对主动脉LDL聚焦蓄积的作用。氧化LDL（弱阴离子化）、去唾液酸LDL（弱阳离子化）和还原甲基化LDL（净电荷无变化）都聚焦蓄积。在喂食普罗布考以抑制LDL氧化的球囊扩张兔中，天然LDL也发生了聚焦蓄积。强阴离子化的琥珀酰化和重氮苯胂化LDL以及强阳离子化的二甲基丙二胺LDL没有聚焦蓄积。结果支持这样的概念，即动脉病变中LDL的聚焦隔离是由LDL上特定的、与氧化无关的电荷和极性模式介导的，而这些模式会因LDL表面电荷的重大变化而被破坏。
