Bremner W F, Third J L, Clark B, Corstorphine C, Lawrie T D
Atherosclerosis. 1978 Mar;29(3):291-9. doi: 10.1016/0021-9150(78)90077-1.
A simple procedure has been devised to give virtually pure preparations of polymorphonuclear leucocytes. This has permitted study of the regulation of cholesterol biosynthesis at cell level. Freshly isolated cells from donors with various forms of hyperlipoproteinaemia have been shown to have very low levels of cholesterol synthesis, presumably due to high circulating levels of apoprotein-B in donor plasma [1]. The activity of the rate-limiting enzyme for cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase, rapidly increases as the cells are incubated in lipoprotein-deficient medium, until, by 12 h, cells from patients heterozygous for familial type IIa hypercholesterolaemia are clearly distinguished from other hyperlipoproteinaemias. The possible significance of this finding is discussed in relation to the causation and treatment of atherosclerotic disease.
已设计出一种简单的程序来制备几乎纯净的多形核白细胞制剂。这使得在细胞水平上研究胆固醇生物合成的调节成为可能。来自患有各种形式高脂蛋白血症的供体的新鲜分离细胞已被证明胆固醇合成水平非常低,这可能是由于供体血浆中载脂蛋白B的循环水平较高[1]。胆固醇生物合成的限速酶3-羟基-3-甲基戊二酰辅酶A还原酶的活性在细胞于无脂蛋白培养基中孵育时迅速增加,直到12小时后,家族性IIa型高胆固醇血症杂合子患者的细胞与其他高脂蛋白血症患者的细胞明显区分开来。结合动脉粥样硬化疾病的病因和治疗讨论了这一发现的可能意义。