Genetics
LDL particles from CETP-deficient patients bind LDL receptors two to three times less avidly than normal LDL (Eur J Clin Invest 1995)
Original title: Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency
Building on prior work showing that CETP-deficient hyperalphalipoproteinaemic patients have polydisperse LDL and cholesterol-enriched, HDLc-like HDL particles, this study tested how authentic LDL from these patients interacts with LDL receptors on normal human fibroblasts. After removing HDLc-like particles from the ultracentrifugally isolated LDL fraction by anti-apoA-I immunoaffinity chromatography, the remaining authentic LDL from CETP-deficient patients was deficient in cholesteryl ester and rich in triglycerides and apoB, ranging in size from 23 to 30 nm. In a competitive binding assay against radiolabeled normal LDL, the concentration of patient LDL needed to displace 50% of labeled LDL from fibroblast LDL receptors was two to three times higher than for control LDL, indicating reduced receptor affinity. The authors conclude that CETP may play an important role in making LDL particles homogeneous and cholesteryl ester-rich.
Original abstract
We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinaemic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the polydisperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)-like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 g mL-1) from the CETP-deficient patients contained HDLc-like particles, these particles were removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with 125I-labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of 125I-labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE.(ABSTRACT TRUNCATED AT 250 WORDS)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.