Pieters M N, Castro G R, Schouten D, Duchateau P, Fruchart J C, Van Berkel T J
Division of Biopharmaceutics, Sylvius Laboratory, University of Leiden, The Netherlands.
Biochem J. 1993 Jun 15;292 ( Pt 3)(Pt 3):819-23. doi: 10.1042/bj2920819.
High-density lipoprotein (HDL) subclass LpA-I has been reported to promote cholesterol efflux from mouse adipose cells in vitro, whereas subclass LpA-I/A-II has no effect. To investigate whether the apolipoprotein composition of HDL plays a role in the selective delivery of cholesterol esters to the liver in vivo, we labelled HDL in its cholesterol ester moiety and separated [3H]cholesterol oleate-labelled HDL into subclasses LpA-I and LpA-I/A-II by immuno-affinity chromatography. Serum decay and liver association of LpA-I and LpA-I/A-II were compared for the apoprotein and cholesterol ester moieties. Both LpA-I and LpA-I/A-II selectively delivered cholesterol esters to the liver with similar kinetics. The kinetics of biliary secretion of processed cholesterol esters, initially associated with LpA-I or LpA-I/A-II, were studied in rats equipped with permanent catheters in bile, duodenum and heart. For both LpA-I and LpA-I/A-II, liver association was coupled to bile acid synthesis, with an increase in secretion rate during the night. During the first night period, the biliary secretion of LpA-I-derived radio-activity was significantly greater than for LpA-I/A-II. The data indicate that with both LpA-I and LpA-I/A-II selective delivery of cholesterol esters from HDL to the liver occurs, but that cholesterol esters delivered by LpA-I are more efficiently coupled to bile acid synthesis.
据报道，高密度脂蛋白（HDL）亚类LpA-I可促进小鼠脂肪细胞在体外的胆固醇流出，而亚类LpA-I/A-II则无此作用。为了研究HDL的载脂蛋白组成在体内胆固醇酯向肝脏的选择性输送中是否起作用，我们在其胆固醇酯部分标记了HDL，并通过免疫亲和色谱法将[3H]胆固醇油酸酯标记的HDL分离为LpA-I和LpA-I/A-II亚类。比较了LpA-I和LpA-I/A-II的载脂蛋白和胆固醇酯部分的血清衰变和肝脏结合情况。LpA-I和LpA-I/A-II均以相似的动力学将胆固醇酯选择性地输送到肝脏。在配备了永久性胆管、十二指肠和心脏导管的大鼠中，研究了最初与LpA-I或LpA-I/A-II相关的加工后胆固醇酯的胆汁分泌动力学。对于LpA-I和LpA-I/A-II，肝脏结合均与胆汁酸合成相关，夜间分泌率增加。在第一个夜间期间，LpA-I衍生的放射性物质的胆汁分泌明显大于LpA-I/A-II。数据表明，LpA-I和LpA-I/A-II均可将HDL中的胆固醇酯选择性输送到肝脏，但LpA-I输送的胆固醇酯与胆汁酸合成的耦合效率更高。
