Chung B H, Franklin F, Cho B H, Segrest J P, Hart K, Darnell B E
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Arterioscler Thromb Vasc Biol. 1998 Aug;18(8):1217-30. doi: 10.1161/01.atv.18.8.1217.
To investigate the role of various lipoproteins in plasma to promote cholesterol efflux from cell membranes, potencies of lipoproteins in normolipidemic fasting and postprandial (PP) plasmas to accept additional cholesterol molecules from cell membranes were determined. We used red blood cells (RBCs) and lipoproteins in fresh blood as donors and acceptors of cell membrane cholesterol, respectively. When fresh fasting plasma (n=24) containing active lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer proteins (CETP) was incubated with a 3-fold excess of autologous RBCs at 37 degrees C for 18 hours, plasma cholesterol levels increased by 19.6% (38.5+/-14.2 mg/dL) owing to an exclusive increase in the CE level. Very low density lipoprotein (VLDL), low density lipoprotein (LDL), and high density lipoprotein (HDL) fractions retained 48.1%, 26.3%, and 25.6% of the net cholesterol mass increase in fasting plasma, resulting in 91%, 8%, and 21% increases in their cholesterol contents, respectively. The PP plasma was 1.3-fold more potent than fasting plasma in promoting cholesterol efflux from RBCs by associating excess cholesterol with chylomicrons, resulting in a 356% increase in the cholesterol content of chylomicrons. These increases in lipoprotein cholesterol content indicate that chylomicrons were about 3.9x, 44x, and 17x more potent than fasting VLDL, LDL, and HDL, respectively, in accepting additional cholesterol molecules released from RBCs. The capacity of PP plasma to promote cholesterol efflux from RBCs was significantly correlated with plasma cholesterol levels (r=0.60, P<0.005), triglycerides (r=0.68, P<0.001), chylomicrons (r=0.90, P<0.001), VLDL (r=0.65, P<0.001), and LDL (r=0.47, P<0.025) but not with the levels of HDL (r= -0.34, P<0.20). In fasting plasma containing a low level of VLDL and HDL, isolated chylomicrons supplemented to the plasma were approximately 9x more potent than HDL in boosting the capacity of plasma to promote cholesterol efflux from RBCs. This study indicates that chylomicrons in PP plasma are the most potent ultimate acceptors of cholesterol released from cell membranes and that a low HDL level is not a factor that limits the ability of PP plasma to promote cholesterol efflux from cell membranes. Our data obtained from an in-vitro system suggest that PP chylomicrons may play a major role in promoting reverse cholesterol transport in vivo, since the transfer of cholesterol from cell membranes to chylomicrons will lead to the rapid removal of this cholesterol by the liver. HDL in vivo may promote reverse cholesterol transport by enhancing the rapid removal of chylomicrons from the circulation, since the rate of clearance of chylomicrons is positively correlated with the HDL level in plasma.
为研究血浆中各种脂蛋白在促进胆固醇从细胞膜流出方面的作用，我们测定了正常血脂的空腹和餐后（PP）血浆中脂蛋白从细胞膜接受额外胆固醇分子的能力。我们分别将新鲜血液中的红细胞（RBC）和脂蛋白用作细胞膜胆固醇的供体和受体。当含有活性卵磷脂：胆固醇酰基转移酶（LCAT）和胆固醇酯转运蛋白（CETP）的新鲜空腹血浆（n = 24）与3倍过量的自体红细胞在37℃孵育18小时时，由于CE水平的单独升高，血浆胆固醇水平升高了19.6%（38.5±14.2mg/dL）。极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白（HDL）组分分别保留了空腹血浆中净胆固醇质量增加的48.1%、26.3%和25.6%，导致其胆固醇含量分别增加了91%、8%和21%。PP血浆在通过将过量胆固醇与乳糜微粒结合来促进红细胞胆固醇流出方面比空腹血浆强1.3倍，导致乳糜微粒的胆固醇含量增加了356%。这些脂蛋白胆固醇含量的增加表明，乳糜微粒在接受从红细胞释放的额外胆固醇分子方面分别比空腹VLDL、LDL和HDL强约3.9倍、44倍和17倍。PP血浆促进红细胞胆固醇流出的能力与血浆胆固醇水平（r = 0.60，P < 0.005）、甘油三酯（r = 0.68，P < 0.001）、乳糜微粒（r = 0.90，P < 0.001）、VLDL（r = 0.65，P < 0.001）和LDL（r = 0.47，P < 0.025）显著相关，但与HDL水平（r = -0.34，P < 0.20）无关。在含有低水平VLDL和HDL的空腹血浆中，添加到血浆中的分离乳糜微粒在增强血浆促进红细胞胆固醇流出的能力方面比HDL强约9倍。这项研究表明，PP血浆中的乳糜微粒是从细胞膜释放的胆固醇的最有效最终受体，并且低HDL水平不是限制PP血浆促进细胞膜胆固醇流出能力的因素。我们从体外系统获得的数据表明，PP乳糜微粒可能在体内促进胆固醇逆向转运中起主要作用，因为胆固醇从细胞膜向乳糜微粒的转移将导致肝脏快速清除这种胆固醇。体内HDL可能通过增强乳糜微粒从循环中的快速清除来促进胆固醇逆向转运，因为乳糜微粒的清除率与血浆中HDL水平呈正相关。
