Alexander J J, Hoenig M, Graham D, Imbembo A L
Case Western Reserve University School of Medicine, Cleveland, Ohio.
Surgery. 1989 Aug;106(2):386-90; discussion 391.
The inhibition of atherosclerosis by estrogen has been shown clinically and experimentally, but the mechanism by which this occurs is unknown. Previous studies have shown that estrogen enhances the uptake of low-density lipoprotein (LDL) by bovine aortic endothelial cells (BAEC) while not altering membrane binding at saturating levels of LDL. In this study the effect of estrogen on LDL binding kinetics has been investigated. Computer-assisted Scatchard analysis of binding data suggests a single-site binding model. Estrogen-treated BAEC showed a lower binding affinity (Ka = 2.47 +/- 0.74 E7 M-1) than control cells (1.95 +/- 0.21 E7 M-1) (p = 0.0012). Estrogen-treated cells, however, had a greater binding capacity (Bmax = 1.26 +/- 0.07 E-10M) than control cells (Bmax = 8.49 +/- 0.44 E-11M) (p = 0.0004). The latter was due primarily to a difference in LDL binding at higher concentrations of LDL (greater than 40 micrograms/ml). These findings are consistent with an estrogen-stimulated increase in low-affinity binding of LDL to BAEC, which may not be directly receptor mediated and which appears to enhance the uptake of LDL at higher lipoprotein concentrations. Such alterations in LDL uptake by endothelial cells could influence the formation of atherosclerotic plaque.
雌激素对动脉粥样硬化的抑制作用已在临床和实验中得到证实，但其发生机制尚不清楚。先前的研究表明，雌激素可增强牛主动脉内皮细胞（BAEC）对低密度脂蛋白（LDL）的摄取，而在LDL饱和水平时不改变膜结合。在本研究中，研究了雌激素对LDL结合动力学的影响。结合数据的计算机辅助Scatchard分析表明存在单位点结合模型。经雌激素处理的BAEC显示出比对照细胞更低的结合亲和力（Ka = 2.47 +/- 0.74 E7 M-1）（对照细胞为1.95 +/- 0.21 E7 M-1）（p = 0.0012）。然而，经雌激素处理的细胞具有比对照细胞更大的结合能力（Bmax = 1.26 +/- 0.07 E-10M）（对照细胞的Bmax = 8.49 +/- 0.44 E-11M）（p = 0.0004）。后者主要是由于在较高浓度的LDL（大于40微克/毫升）下LDL结合的差异。这些发现与雌激素刺激LDL与BAEC的低亲和力结合增加一致，这可能不是直接由受体介导的，并且似乎在较高脂蛋白浓度下增强了LDL的摄取。内皮细胞对LDL摄取的这种改变可能会影响动脉粥样硬化斑块的形成。
