Brown M S, Kovanen P T, Goldstein J L
Ann N Y Acad Sci. 1980;348:48-68. doi: 10.1111/j.1749-6632.1980.tb21290.x.
The initial observations in cultured fibroblasts made six years ago allowed the formulation of a series of hypotheses concerning LDL metabolism in tissues of animals and man. The most important of these hypotheses was that a large fraction of LDL was removed from plasma by a specific receptor-mediated uptake mechanism whose function was to supply cholesterol to extrahepatic cells. This hypothesis is strongly supported by genetic observations in patients with familial hypercholesterolemia and by studies of the four model systems discussed above. These studies by no means solve all of the important questions about LDL metabolism. We still need to know which tissues take up the most LDL; we need to know how much LDL is cleared by the liver and whether this clearance involves the same LDL receptor that operates in extra-hepatic cells; we need to know the mechanism for the clearance of the one-half to two-thirds of LDL that leaves the plasma by receptor-independent pathways; and finally we need to know how an abnormal accumulation of LDL in the plasma leads to the deposition of cholesterol in scavenger cells and produces atherosclerosis.
六年前在培养的成纤维细胞中进行的初步观察，使得一系列关于动物和人类组织中低密度脂蛋白（LDL）代谢的假说得以形成。这些假说中最重要的一点是，很大一部分LDL是通过一种特定的受体介导摄取机制从血浆中清除的，其功能是为肝外细胞提供胆固醇。家族性高胆固醇血症患者的遗传学观察以及上述四种模型系统的研究，都有力地支持了这一假说。这些研究远未解决所有关于LDL代谢的重要问题。我们仍然需要知道哪些组织摄取的LDL最多；我们需要知道肝脏清除了多少LDL，以及这种清除是否涉及在肝外细胞中起作用的相同LDL受体；我们需要知道通过非受体依赖途径离开血浆的LDL的一半到三分之二的清除机制；最后，我们需要知道血浆中LDL的异常积累是如何导致胆固醇在吞噬细胞中沉积并产生动脉粥样硬化的。
