Genetics
ApoE-rich HDL that accumulates in CETP deficiency binds the LDL receptor with far higher affinity than LDL itself (J Clin Invest 1990)
Original title: Accumulation of apolipoprotein E-rich high density lipoproteins in hyperalphalipoproteinemic human subjects with plasma cholesteryl ester transfer protein deficiency
Comparing hyperalphalipoproteinemic patients with and without CETP deficiency, subjects with CETP deficiency had elevated apolipoprotein E that correlated with the appearance of apoE-rich HDL particles containing predominantly apoE (82%) and little apoA-I (18%). These apoE-rich HDL particles bound LDL receptors on human fibroblasts with much higher affinity than human LDL, and 3.5 times fewer apoE-rich HDL particles than LDL were needed to saturate the receptors, indicating each particle engages the LDL receptor through multiple apoE copies. These particles, resembling cholesterol-induced apoE HDLc, were absent in normal subjects and in hyperalphalipoproteinemic subjects with normal CETP activity, whose apoE-containing HDL were smaller and carried only 14% apoE, establishing a correlation between CETP level and the emergence of this distinctive apoE-rich HDL species.
Original abstract
This study characterized the plasma lipoproteins of familial hyperalphalipoproteinemic patients with or without deficiency of cholesteryl ester transfer protein (CETP) activity. The subjects with CETP deficiency have increased levels of apolipoprotein (apo) E. The increased concentration of apo E in these subjects was correlated to the appearance of apo E-rich high density lipoproteins (HDL). Sodium dodecyl sulfate-polyacrylamide gel analysis revealed that these lipoproteins contained predominantly the apo E (82%) and little amount of apo A-I (18%). These apo E-rich HDL displayed a much higher affinity than human LDL in binding to LDL receptors on human fibroblasts. Furthermore, 3.5 times fewer apo E-rich HDL than LDL were required to saturate the receptors on fibroblasts. These data indicated that the apo E-rich HDL in CETP-deficient human subjects contained multiple copies of apo E and bound to the LDL receptor through multiple interactions. The apo E-rich HDL, with similar properties as cholesterol-induced apo E HDLc, were not detectable in normal human subjects or in hyperalphalipoproteinemic subjects with normal CETP activity. The apo E-containing HDL in the latter subjects were smaller and contained only small amounts of apo E (14%). The difference in apo E-containing HDL in these subjects suggests a correlation between CETP level and the appearance of apo E-rich HDL.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.