Dresel H A, Friedrich E A, Otto I, Waldherr R, Schettler G
Arzneimittelforschung. 1985;35(12A):1936-40.
In man and in experimental animals, elevations in plasma cholesterol lead to premature atherosclerosis. It is likely that the cholesterol-rich low density lipoprotein (LDL) plays a keyrole in atherogenesis. LDL accumulates in patients with familial hypercholesterolemia (FH), a genetic syndrome associated with a defective LDL receptor in parenchymal cells and premature atherosclerosis. Monocytic/macrophage-like cells invading the vessel wall are becoming enriched with cholesteryl ester and concentrating in the early atherosclerotic lesion. Modification of LDL stimulates the uptake of cholesterol by macrophages in vitro leading to the conversion of the cells to lipid laden foam cells. Because of this phenomenon recent investigations were focussing on the lipid metabolism of macrophages. In vitro studies have demonstrated that macrophages have specific cell surface receptors for modified forms of LDL. It was suggested that these scavenger receptors could mediate foam cell formation in vivo, too. In vivo analysis by sequential scintiscans revealed that the liver is accumulating most actively modified LDL, possibly acting as a sieve for atherogenic lipoproteins. The putative liver receptor for modified (= atherogenic) LDL was characterized as a membrane protein of 220 000 to 250 000 D by ligand blotting.
在人类和实验动物中，血浆胆固醇升高会导致动脉粥样硬化提前发生。富含胆固醇的低密度脂蛋白（LDL）可能在动脉粥样硬化形成过程中起关键作用。LDL在家族性高胆固醇血症（FH）患者中蓄积，FH是一种与实质细胞中LDL受体缺陷及动脉粥样硬化提前发生相关的遗传综合征。侵入血管壁的单核细胞/巨噬细胞样细胞富含胆固醇酯，并聚集在早期动脉粥样硬化病变中。LDL的修饰会刺激巨噬细胞在体外摄取胆固醇，导致细胞转变为充满脂质的泡沫细胞。由于这种现象，最近的研究集中在巨噬细胞的脂质代谢上。体外研究表明，巨噬细胞具有针对修饰形式LDL的特异性细胞表面受体。有人提出，这些清道夫受体也可能在体内介导泡沫细胞的形成。通过连续闪烁扫描进行的体内分析显示，肝脏最活跃地蓄积修饰后的LDL，可能起到了对致动脉粥样硬化脂蛋白进行筛选的作用。通过配体印迹法，将推测的肝脏修饰（即致动脉粥样硬化）LDL受体鉴定为一种分子量为220 000至250 000 D的膜蛋白。
