HDL biology
Desialylation of lipoproteins boosts CETP-mediated cholesteryl ester transfer from HDL while impairing reverse cholesterol transport (Atherosclerosis 1998)
Original title: Lipoprotein desialylation simultaneously enhances the cell cholesterol uptake and impairs the reverse cholesterol transport system: in vitro evidences utilizing neuraminidase-treated lipoproteins and mouse peritoneal macrophages
Using neuraminidase-treated (desialylated) VLDL, LDL, total HDL, and HDL2/HDL3 subfractions isolated from healthy donor plasma, incubated in vitro with mouse peritoneal macrophages, the effects of lipoprotein desialylation on cholesterol handling were investigated. Desialylation significantly decreased the capacity of total HDL and HDL2, but not HDL3, to efflux cellular cholesterol, and lowered the LCAT-mediated cholesterol esterification rate without changing the intrinsic LCAT activity of HDL. Desialylation also increased CETP-mediated cholesteryl ester transfer from HDL to apolipoprotein B-containing lipoproteins, and enhanced macrophage uptake of cholesterol from both HDL and LDL, with considerably greater uptake from desialylated LDL than from desialylated HDL. The authors conclude that lipoprotein desialylation may contribute to premature atherosclerosis both by enhancing cellular cholesterol uptake and by impairing the reverse cholesterol transport system, in part through increased CETP-mediated transfer.
Original abstract
Desialylation of low density lipoprotein (LDL) brings about accumulation of cholesterol in cultured cells. The influence of the neuraminidase-treated lipoprotein (LP) on the reverse cholesterol transport system was investigated in vitro utilizing very low density lipoprotein (VLDL), LDL, total high density lipoprotein (HDL) and its subfractions, HDL2 and HDL3, isolated from healthy donor plasma and mouse peritoneal macrophages. It was found that LP desialylation significantly: (1) decreased the capacity of total HDL and of HDL2, but not of HDL3, to efflux cellular cholesterol; (2) lowered the cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT) without modifying the intrinsic LCAT activity of HDL; (3) increased the cholesteryl ester transfer from HDL to apo B-containing LP mediated by cholesteryl ester transfer protein (CETP); (4) enhanced the uptake by macrophages of cholesterol from HDL and LDL, although the amount of cholesterol taken up by the cells was much greater from the desialylated LDL than from desialylated HDL. Taken together, these in vitro evidences indicate that, in addition to enhancing the cell cholesterol LP uptake, desialylation may contribute to the premature development of atherosclerosis by impairing the reverse cholesterol transport system.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.