COMPETITIVE-INHIBITION OF LDL BINDING AND UPTAKE BY HDL IN AORTIC ENDOTHELIAL-CELLS
COMPETITIVE-INHIBITION OF LDL BINDING AND UPTAKE BY HDL IN AORTIC ENDOTHELIAL-CELLS
复制标题
DOI：
10.1016/0022-4804(90)90128-o
复制
发表时间：
1990-09-01
影响因子：
2.2
通讯作者：
GRAHAM, D
中科院分区：
文献类型：
--
作者：
ALEXANDER, JJ;MIGUEL, R;GRAHAM, D
高密度脂蛋白（HDL）可以抑制低密度脂蛋白（LDL）的结合和细胞摄取，作为调节外源性胆固醇向非肝组织递送的一种手段。这可能通过改变动脉壁细胞中的脂质代谢在动脉粥样硬化形成中起重要作用。为了验证和更好地表征这种作用，从牛主动脉收获内皮细胞并保持在组织培养物中。在缺乏脂质的培养基中初始预温育后，将这些细胞在4 ℃温育2小时。C在含有125 I-LDL（10 μ g蛋白质/ml）和不同浓度的HDL（0-400 μ g蛋白质/ml）或相当量的载脂蛋白A（Apo A）（HDL的主要蛋白质组分）的培养基中。分别测定细胞内和胰蛋白酶释放计数，分别作为细胞摄取和膜结合LDL的测量。本研究的结果表明HDL抑制LDL结合和摄取（P < 0.005，ANOVA）。ApoA单独使用也有类似的抑制作用（P < 0.005）。当使用125 I-Apoprotein B（LDL的蛋白组分）和Apo A进行相同的研究时，发现后者以相同的程度抑制Apo B的结合（P < 0.0006）。这些结果表明，HDL确实抑制牛主动脉内皮细胞对LDL的结合和摄取，并且由于这种作用仅与这些脂蛋白颗粒的蛋白质组分相同，因此最有可能是由于受体水平的竞争性结合，而不是硬脂酸阻碍或细胞膜的改变。
High-density lipoprotein (HDL) may inhibit the binding and cellular uptake of low-density lipoprotein (LDL) as one means of regulating the delivery of exogenous cholesterol to nonhepatic tissues. This may play an important role in atherogenesis, by altering lipid metabolism in cells of the arterial wall. To verify and better characterize this effect, endothelial cells were harvested from bovine aorta and maintained in tissue culture. Following initial preincubation in lipid-deficient culture media, these cells were incubated for 2 hr at 4.degree. C in media containing 125I-LDL (10 .mu.g protein/ml) and varying concentrations of either HDL (0-400 .mu.g protein/ml) or comparable amounts of Apoprotein A (Apo A), the major protein component of HDL. Intracellular and trypsin-released counts were assayed separately, as a measurement of cellular uptake and membrane bound LDL, respectively. Results of this study indicated an inhibition of LDL binding and uptake by HDL (P < 0.005, ANOVA). A similar inhibition was found with Apo A alone (P < 0.005). When identical studies were performed using 125I-Apoprotein B, the protein component of LDL, and Apo A, the latter was found to inhibit the binding of Apo B to the same extent (P < 0.0006). These results indicate that HDL does inhibit LDL binding and uptake by bovine aortic endothelial cells and that, because this effect is seen equally with only the protein component of these lipoprotein particles, it is most likely due to competitive binding at the receptor level rather than to stearic hindrance or an alteration of the cell membrane.