LDL and apoB
Normal CETP activity in hypertriglyceridemic patients rules out CETP as the cause of reduced LDL receptor binding affinity (Atherosclerosis 1999)
Original title: Low density lipoprotein (LDL) binding affinity for the LDL receptor in hyperlipoproteinemia
LDL receptor binding affinity was measured in normolipidemic controls and patients with various hyperlipoproteinemia types. Patients with hypertriglyceridemia (type IIb and IV) had LDL with reduced receptor affinity that paralleled triglyceride severity, and their LDL was protein- and triglyceride-rich, cholesterol- and phospholipid-poor, and smaller than normal, resembling small dense LDL; lipid-lowering therapy normalized both LDL characteristics and receptor affinity together. Although reduced CETP activity has been reported to generate small LDL, plasma CETP activity was measured and found to be normal in these hyperlipoproteinemic patients, and drug-induced normalization of LDL characteristics was not accompanied by any increase in CETP activity. The authors conclude that abnormal LDL lipid composition and particle size, rather than CETP activity, explain the reduced receptor affinity.
Original abstract
We measured the binding affinity of low density lipoprotein (LDL) for the LDL receptor in patients with various types of hyperlipoproteinemia and investigated the effects of LDL lipid composition and particle size on receptor affinity. LDL (1.019 < d < 1.063) was isolated by sequential ultracentrifugation from the serum of normolipidemic controls and patients with hyperlipoproteinemia. Patients with type IIa hyperlipoproteinemia had LDL with a similar receptor affinity to that of normal LDL. However, patients with hypertriglyceridemia (type IIb and type IV hyperlipoproteinemia) had LDL with a low receptor affinity, and the degree of the reduction in affinity paralleled the severity of the hypertriglyceridemia. The LDL of hypertriglyceridemic patients was rich in protein and triglycerides, had a low content of cholesterol and phospholipids, and was smaller than normal, thus resembling the atherogenic lipoprotein known as small, dense LDL. These abnormalities were observed even in patients with mild hypertriglyceridemia regardless of their serum cholesterol levels. The degree of alteration in LDL lipid composition and particle size was strongly associated with the reduction of LDL receptor affinity. We also examined the effects of two lipid-lowering agents (bezafibrate and probucol) on the characteristics of LDL. LDL receptor affinity was only improved when the lipid composition and particle size were normalized by drug therapy. Although it has been reported that decreased cholesteryl ester transfer protein (CETP) activity results in the formation of small LDL, plasma CETP activity was normal in the hyperlipoproteinemic patients and the normalization of LDL characteristics by drug therapy was not accompanied by an increase of CETP activity. Our results suggested that an abnormal lipid composition and/or small particle size might cause a decrease in the receptor affinity of LDL. These structural and functional abnormalities were reversed by drug therapy, underlining the importance of treating hypertriglyceridemia for the prevention of atherosclerosis.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.