HOW LDL RECEPTORS INFLUENCE CHOLESTEROL AND ATHEROSCLEROSIS
HOW LDL RECEPTORS INFLUENCE CHOLESTEROL AND ATHEROSCLEROSIS
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DOI：
10.1038/scientificamerican1184-58
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发表时间：
1984-01-01
影响因子：
3
通讯作者：
GOLDSTEIN, JL
中科院分区：
文献类型：
--
作者：
BROWN, MS;GOLDSTEIN, JL
在美国，一半的死亡是由动脉粥样硬化引起的，在这种疾病中，胆固醇在动脉壁中积聚，形成大块斑块，抑制血液流动，直至最终形成凝块，阻塞动脉并导致心脏病发作或中风。动脉粥样硬化斑块中的胆固醇源自血液中循环的低密度脂蛋白 (LDL) 颗粒。血液中的低密度脂蛋白越多，动脉粥样硬化发展得越快。流行病学数据揭示了一个令人惊讶的事实，即包括美国在内的西方工业化社会中，超过一半的人循环中的低密度脂蛋白水平很高，使他们面临发生动脉粥样硬化的高风险。由于这种浓度如此普遍，因此它们被认为是“正常”，但显然它们并不是真正的正常。它们容易加速动脉粥样硬化和心脏病或中风。是什么决定了血液中的低密度脂蛋白水平，为什么很多美国人的低密度脂蛋白水平都处于危险的水平？对特殊蛋白质（称为低密度脂蛋白受体）的研究中出现了一些答案，这种蛋白质从动物细胞表面突出。受体结合低密度脂蛋白颗粒，并将它们从沐浴细胞的液体中提取出来。低密度脂蛋白被吸收到细胞中并分解，产生胆固醇以满足每个细胞的需要。在为细胞提供胆固醇的过程中，受体执行第二个生理功能，这对动脉粥样硬化的发展至关重要：它们从血液中清除低密度脂蛋白。细胞表面的受体数量随细胞对胆固醇的需求而变化。当需要量低时，多余的胆固醇就会积累；当需要量低时，多余的胆固醇就会积聚起来。细胞产生的受体减少，吸收低密度脂蛋白的速度也降低。这可以保护细胞免受过量胆固醇的影响，但代价很高：受体数量的减少降低了低密度脂蛋白从循环中清除的速度，
Half of all deaths in the US are caused by atherosclerosis, the disease in which cholesterol, ac cumulating in the wall of arteries, forms bulky plaques that inhibit the flow of blood until a clot eventually forms, ob structing an artery and causing a heart attack or a stroke. The cholesterol of atherosclerotic plaq ues is derived from particles called low-density lipoprotein (LDL) that circulate in the bloodstream. The more LDL there is in the blood, the more rapidly atherosclerosis develops. Epidemiologic data reveal the sur prising fact that more than half of the people in Western industrialized socie ties, including the US, have a level of circulating LDL that puts them at high risk for developing atherosclerosis. Be cause such concentrations are so preva lent, they are considered" normal," but clearly they are not truly normal. They predispose to accelerated atherosclero sis and heart attacks or strokes. What determines the blood level of LDL, and why is the level dangerously high in so many Americans? Some an swers are emerging from studies of spe cialized proteins, called LDL receptors, that project from the surface of animal cells. The receptors bind LDL particles and extract them from the fI uid that bathes the cells. The LDL is taken into the cells and broken down, yielding its cholesterol to serve each cell's needs. In supplying cells with cholesterol the re ceptors perform a second physiological function, which is critical to the devel opment of atherosclerosis: they remove LDL from the bloodstream. The number of receptors displayed on the surface of cells varies with the cells' demand for cholesterol. When the need is low, excess cholesterol accumulates; cells make fewer receptors and take up LDL at a red uced rate. This protects cells against excess cholesterol, but at a high price: the reduction in the number of receptors decreases the rate at which LDL is removed from the circulation,