McPherson R, Agnani G, Lau P, Fruchart J C, Edgar A D, Marcel Y L
University of Ottawa Heart Institute, Canada.
Arterioscler Thromb Vasc Biol. 1996 Nov;16(11):1340-6. doi: 10.1161/01.atv.16.11.1340.
The two major subclasses of HDL contain apo A-I only (Lp A-I) or both apo A-I and apo A-II (Lp A-I/A-II). We have carried out experiments to quantify the participation of Lp A-I and Lp A-I/A-II in the neutral lipid transfer reaction in normal and hypertriglyceridemic subjects. Thirteen hypertriglyceridemic subjects were studied before and after fenofibrate therapy. Fenofibrate treatment resulted in decreases in total cholesterol, triglycerides (TG), and VLDL cholesterol of 19%, 48%, and 70%, respectively, and a 28% increase in HDL cholesterol, with no significant change in the proportion of Lp A-I and Lp A-I/A-II particles. The abundance of cholesteryl ester transfer protein (CETP) mRNA in peripheral adipose tissue decreased with treatment in four of five patients studied; however, no change occurred in plasma CETP mass. Using an isotopic transfer assay, we demonstrated that both Lp A-I and Lp A-I/A-II participated in the CE transfer reaction, with no change after fenofibrate therapy. This finding suggests that the marked increase in HDL cholesterol during fenofibrate therapy is due to normalization of plasma TG and hence decreased opportunity for mass transfer of lipid between HDL and TG-rich proteins in vivo. In this population of hypertriglyceridemic subjects, CETP was distributed in both the Lp A-I and Lp A-I/A-II subfractions of HDL, with preferential association with the smaller Lp A-I poor. In contrast, in nine normal subjects studied, negligible amounts of CETP were associated with Lp A-I/A-II. Nonetheless, the Lp A-I/A-II fraction of HDL contributed significantly to total CE mass transfer in normolipidemic plasma. Lp A-I/A-II is an efficient donor for CE transfer to TG-rich lipoproteins, and its low affinity for CETP may in fact facilitate neutral lipid transfer either by a shuttle mechanism or by formation of a ternary complex.
高密度脂蛋白（HDL）的两个主要亚类仅包含载脂蛋白A-I（Lp A-I）或同时包含载脂蛋白A-I和载脂蛋白A-II（Lp A-I/A-II）。我们进行了实验，以量化Lp A-I和Lp A-I/A-II在正常和高甘油三酯血症受试者中性脂质转移反应中的参与情况。对13名高甘油三酯血症受试者在非诺贝特治疗前后进行了研究。非诺贝特治疗使总胆固醇、甘油三酯（TG）和极低密度脂蛋白胆固醇分别降低了19%、48%和70%，高密度脂蛋白胆固醇增加了28%，而Lp A-I和Lp A-I/A-II颗粒的比例没有显著变化。在研究的5名患者中，有4名患者外周脂肪组织中胆固醇酯转移蛋白（CETP）mRNA的丰度随治疗而降低；然而，血浆CETP质量没有变化。使用同位素转移测定法，我们证明Lp A-I和Lp A-I/A-II都参与了胆固醇酯（CE）转移反应，非诺贝特治疗后没有变化。这一发现表明，非诺贝特治疗期间高密度脂蛋白胆固醇的显著增加是由于血浆TG正常化，因此体内HDL与富含TG的蛋白质之间脂质大量转移的机会减少。在这群高甘油三酯血症受试者中，CETP分布在HDL的Lp A-I和Lp A-I/A-II亚组分中，优先与较小的、Lp A-I含量低的亚组分结合。相比之下，在研究的9名正常受试者中，与Lp A-I/A-II相关的CETP量可忽略不计。尽管如此，HDL的Lp A-I/A-II组分对正常血脂血浆中的总CE质量转移有显著贡献。Lp A-I/A-II是CE转移至富含TG的脂蛋白的有效供体，其对CETP的低亲和力实际上可能通过穿梭机制或形成三元复合物促进中性脂质转移。
