Fielding P E, Vlodavsky I, Gospodarowicz D, Fielding C J
J Biol Chem. 1979 Feb 10;254(3):749-55.
Cholesterol synthesis in actively growing bovine vascular endothelial cells is regulated by low density lipoprotein (LDL) at a step prior to mevalonate formation, in a manner comparable to that found in aortic smooth muscle cells. LDL uptake by these cells is associated with induction of cholesterol esterification, an increase in total cell cholesterol, and an inhibition of endogenous sterol synthesis. In contrast, cholesterol metabolism in confluent contact-inhibited endothelial cultures was not significantly affected by LDL even though the cells bind the lipoprotein at high affinity receptor sites. Lysosomal degradation and subsequent regulatory effects on cellular cholesterol metabolism, however, were observed in contact-inhibited endothelial cells incubated with cationized rather than native LDL. Cationized LDL enter the cells independently of the high affinity sites. Therefore, the primary regulation of cholesterol metabolism in these cells is neither through the appropriate intracellular enzymes nor through the high affinity surface receptors, but via an inhibition of LDL internalization. It is suggested that this inhibition is due to a strict contact-inhibited morphology which enables the endothelium of the larger arteries to function as a selective barrier to the high circulating levels of plasma LDL.
在活跃生长的牛血管内皮细胞中，胆固醇合成在甲羟戊酸形成之前的一个步骤受到低密度脂蛋白（LDL）的调节，其方式与在主动脉平滑肌细胞中发现的方式类似。这些细胞对LDL的摄取与胆固醇酯化的诱导、细胞总胆固醇的增加以及内源性固醇合成的抑制有关。相比之下，汇合接触抑制的内皮细胞培养物中的胆固醇代谢即使细胞在高亲和力受体位点结合脂蛋白，也不会受到LDL的显著影响。然而，在用阳离子化而非天然LDL孵育的接触抑制内皮细胞中，观察到了溶酶体降解以及随后对细胞胆固醇代谢的调节作用。阳离子化LDL独立于高亲和力位点进入细胞。因此，这些细胞中胆固醇代谢的主要调节既不是通过适当的细胞内酶，也不是通过高亲和力表面受体，而是通过抑制LDL内化。有人认为这种抑制是由于严格的接触抑制形态，这种形态使大动脉的内皮能够作为对高循环水平血浆LDL的选择性屏障发挥作用。
