Chung B H, Segrest J P, Franklin F
Department of Medicine, University of Alabama at Birmingham, 35294, USA.
Atherosclerosis. 1998 Dec;141(2):209-25. doi: 10.1016/s0021-9150(98)00169-5.
As a model for the formation of beta-very low density lipoproteins (VLDL) and small, dense LDL by the intraplasma metabolic activities in vivo, lipoproteins in fresh plasma were interacted in vitro with endogenous lecithin:cholesterol acyltransferase (LCAT) and cholesterylester transfer proteins (CETP) and subsequently with purified lipoprotein lipase (LpL). The LCAT and CETP reactions in a mildly hypertriglyceridemic (HTG) plasma at 37 degrees C for 18 h resulted in (1) esterification of about 45% plasma unesterified cholesterol (UC), (2) a marked increase in cholesterylester (CE) (+129%) and a decrease in triglyceride (TG) (-45%) in VLDL, and (3) a marked increase of TG (+ 341%) with a small net decrease of CE (-3.6%) in LDL, causing a significant alteration in the TG/CE of VLDL (from 8.0 to 1.9) and of LDL (from 0.20 to 0.93). The LDL in LCAT and CETP-reacted plasma is larger and more buoyant than that in control plasma. In vitro lipolysis of control and LCAT and CETP-reacted plasma by LpL, which hydrolyzed >90% of VLDL-TG and about 50-60% of LDL-TG, converted most of VLDL in control plasma (>85%) but less than half (40%) of VLDL in LCAT and CETP-reacted plasma into the IDL-LDL density fraction and transformed the large, buoyant LDL in the LCAT and CETP-reacted plasma into particles smaller and denser than those in the control plasma. The remnants that accumulated in the VLDL density region of the postlipolysis LCAT and CETP-reacted plasma contained apo B-100 and E but little or no detectable apo Cs and consisted of particles having pre-beta and beta-electrophoretic mobilities. The inhibition of LCAT during incubation of plasma, which lessened the extent of alteration in VLDL and LDL core lipids, increased the extent of lipolytic removal of VLDL from the VLDL density region but lowered the extent of alteration in the size and density of LDL. The LCAT, CETP and/or LpL-mediated alterations in the density of LDL in normolipidemic fasting plasma were less pronounced than that in mildly HTG plasma, but they became highly pronounced upon increase of its TG-rich lipoprotein level by the addition of preisolated VLDL or by the induction of postprandial lipemia. Although the effect of LCAT, CETP and LpL reactions in non-circulating plasma in vitro may be different from that in vivo, the above data suggests that the plasma TG-rich lipoprotein level and the extent of intraplasma LCAT, CETP, LpL and likely hepatic lipase (HL) reactions in vivo may play a role in determining the LDL phenotype.
作为体内血浆内代谢活动形成β-极低密度脂蛋白（VLDL）和小而密低密度脂蛋白（LDL）的模型，新鲜血浆中的脂蛋白在体外与内源性卵磷脂胆固醇酰基转移酶（LCAT）和胆固醇酯转移蛋白（CETP）相互作用，随后与纯化的脂蛋白脂肪酶（LpL）相互作用。在37℃下，轻度高甘油三酯血症（HTG）血浆中的LCAT和CETP反应持续18小时，结果如下：（1）约45%的血浆未酯化胆固醇（UC）被酯化；（2）VLDL中胆固醇酯（CE）显著增加（+129%），甘油三酯（TG）减少（-45%）；（3）LDL中TG显著增加（+341%），CE有少量净减少（-3.6%），导致VLDL的TG/CE（从8.0降至1.9）和LDL的TG/CE（从0.20升至0.93）发生显著改变。LCAT和CETP反应后的血浆中的LDL比对照血浆中的更大、浮力更强。用LpL对对照血浆以及LCAT和CETP反应后的血浆进行体外脂解，LpL可水解>90%的VLDL-TG和约50-60%的LDL-TG，对照血浆中大部分VLDL（>85%）但LCAT和CETP反应后的血浆中不到一半（40%）的VLDL转化为中间密度脂蛋白-低密度脂蛋白（IDL-LDL）密度组分，并将LCAT和CETP反应后的血浆中较大、浮力强的LDL转化为比对照血浆中更小、更密的颗粒。脂解后LCAT和CETP反应后的血浆中VLDL密度区域积累的残余物含有载脂蛋白B-100和E，但几乎没有或检测不到载脂蛋白C，由具有前β和β电泳迁移率的颗粒组成。血浆孵育过程中LCAT的抑制减少了VLDL和LDL核心脂质的改变程度，增加了VLDL从VLDL密度区域脂解清除的程度，但降低了LDL大小和密度的改变程度。正常血脂空腹血浆中LCAT、CETP和/或LpL介导的LDL密度改变不如轻度HTG血浆明显，但通过添加预先分离的VLDL或诱导餐后血脂升高使其富含TG的脂蛋白水平增加后，这种改变变得非常明显。尽管体外非循环血浆中LCAT、CETP和LpL反应的效果可能与体内不同，但上述数据表明，体内血浆富含TG的脂蛋白水平以及血浆内LCAT、CETP、LpL以及可能的肝脂酶（HL）反应的程度可能在决定LDL表型中起作用。
