Plasma cholesteryl ester transfer protein is lowered by treatment of hypercholesterolemia with cholestyramine.

Cholestyramine (INN, colestyramine) treatment of subjects with hypercholesterolemia reduced the plasma level of cholesteryl ester transfer protein (CETP) as measured by radioimmunoassay (CETP-RIA) and, as expected, also reduced the levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B. The extent of CETP variation was significant only in the subjects whose LDL cholesterol levels were reduced by more than 25%. Furthermore, CETP-RIA was correlated with total cholesterol, LDL cholesterol, and apolipoprotein B concentrations. Plasma CETP was also measured by an indirect procedure that uses high-density lipoprotein (HDL) 14C-cholesteryl ester and very low-density lipoprotein cholesterol from a pool of plasma donors, and the patient's plasma as the source of CETP. The two procedures for CETP determination correlated well with each other, although the CETP-RIA was more sensitive in the detection of changes of plasma CETP ascribed to cholestyramine (INN, colestyramine) treatment. The rise of plasma HDL cholesterol levels after cholestyramine probably resulted from the reduction of CETP activity.

Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone-deficient adult humans.

The incidence of atherosclerosis is increased in growth hormone (GH) deficient-individuals. Nonetheless, the antiatherogenic benefits of GH replacement therapy remain uncertain. In this study the effect of human recombinant growth hormone (hrGH) replacement therapy administered to GH-deficient adults on the plasma cholesteryl ester transfer protein (CETP) concentration and activity was analyzed. These findings were related to changes in the concentrations of the plasma lipoproteins. The hrGH was administered for 12 mon to human GH-deficient patients (n = 13; 8 men, 5 women). During the study plasma lipoproteins were separated by ultracentrifugation, and plasma cholesterol esterification rate (CER), endogenous CETP activity, and CETP concentration were measured. GH replacement therapy transiently (at 3 mon) lowered plasma concentration of CETP and low density lipoprotein-cholesterol (LDL-C) and raised total triglycerides. Furthermore, hrGH permanently increased both the plasma lipoprotein(a) [Lp(a)] concentration, which is known as atherogenic, and the proportion of cholesteryl ester in the high density lipoprotein2 (HDL2) particles, which is potentially atheroprotective. The simultaneous decrease of the plasma CETP and LDL-C concentrations elicited by hrGH indicated a close relationship between LDL metabolism and the regulation of the CETP gene expression. Endogenous CETP activity and the CER were not modified because these parameters are regulated in opposite ways by plasma levels of triglycerides; that is, CER increased and CETP decreased.

Reverse cholesterol transport in diabetes mellitus.

There are epidemiological data and experimental animal models relating the development of premature atherosclerosis with defects of the reverse cholesterol transport (RCT) system. In this regard, the plasma concentrations of the high density lipoprotein (HDL) subfractions, of cholesteryl ester transfer protein (CETP), as well as the activity of the enzyme lecithin-cholesterol acyl transferase (LCAT) play critical roles. However, there has been plenty of evidence that atherosclerosis in diabetes mellitus (DM) is ascribed to a greater arterial wall cell uptake of modified apoB-containing lipoproteins whereas a primary or predominant defect of the RCT system is still a subject of debate. In other words, in spite of the fact that in DM the composition and rates of metabolism of the HDL particles are greatly altered and display a diminished in vitro efficiency to remove cell cholesterol, definitive in vivo demonstration of the importance of this fact in atherogenesis is lacking. Furthermore, the roles played by LCAT and CETP in RCT in DM are difficult to interpret because the in vitro procedures of measurement utilized have either been inadequate, or inappropriately interpreted. Knock-out or transgenic mice are much needed models to investigate the roles of LCAT, CETP, phospholipid transfer protein (PLTP), and of a CETP inhibitor in the development of atherosclerosis of experimental DM.