HDL biology
LpA-I:A-II is an efficient CE donor to triglyceride-rich lipoproteins despite low CETP affinity, fenofibrate raising HDL cholesterol 28% without changing CETP mass (Arterioscler Thromb Vasc Biol 1996)
Original title: Role of Lp A-I and Lp A-I/A-II in cholesteryl ester transfer protein-mediated neutral lipid transfer. Studies in normal subjects and in hypertriglyceridemic patients before and after fenofibrate therapy
The two major HDL subclasses, containing apoA-I alone (LpA-I) or apoA-I and apoA-II together (LpA-I/A-II), were studied for their participation in CETP-mediated neutral lipid transfer in normal and hypertriglyceridemic subjects. In thirteen hypertriglyceridemic subjects, fenofibrate therapy decreased total cholesterol, triglycerides, and VLDL cholesterol by 19%, 48%, and 70%, respectively, and increased HDL cholesterol by 28%, with no change in LpA-I versus LpA-I/A-II proportions. Adipose tissue CETP mRNA decreased with treatment in 4 of 5 patients, but plasma CETP mass was unchanged. Both LpA-I and LpA-I/A-II participated in cholesteryl ester transfer, unchanged after fenofibrate, suggesting the HDL cholesterol rise reflects normalized plasma triglycerides rather than altered CETP distribution. CETP was distributed across both HDL subfractions in hypertriglyceridemic subjects, but in nine normal subjects CETP was negligibly associated with LpA-I/A-II.
Original abstract
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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.