HDL biology
Review questions whether CETP-mediated cholesterol transfer to apoB lipoproteins undermines the antiatherogenic label of reverse cholesterol transport (Atherosclerosis 1995)
Original title: Is reverse cholesterol transport a misnomer for suggesting its role in the prevention of atheroma formation?
This review examines reverse cholesterol transport, which involves HDL uptake of unesterified cell cholesterol from peripheral tissues including the arterial wall, its esterification by LCAT, direct hepatic uptake of HDL-cholesteryl ester, and an indirect pathway in which CETP transfers HDL-cholesteryl ester to VLDL and LDL. While the direct HDL uptake route is straightforwardly antiatherogenic, the review argues that the CETP-mediated indirect pathway carries ambiguous implications, since it may raise the cholesteryl ester content of apoB-containing lipoproteins that are ultimately taken up by arterial wall macrophages, potentially making it proatherogenic. The review also notes controversial roles played by LCAT and hepatic lipase-mediated hepatic uptake of HDL-cholesteryl ester, and observes that HDL may exert antiatherogenic effects unrelated to cell cholesterol removal altogether.
Original abstract
Reverse cholesterol transport from peripheral tissues, including the arterial wall, involves high density lipoprotein (HDL) uptake of unesterified cell cholesterol, its esterification by lecithin-cholesterol-acyl-transferase (LCAT), direct HDL-cholesteryl ester uptake by the liver and the indirect pathway consisting of the cholesteryl ester transfer protein (CETP)-mediated transfer of HDL-cholesteryl ester to apolipoprotein (apo) B-containing lipoproteins (very low density lipoprotein (VLDL) and LDL). Although the first route should be regarded as anti-atherogenic, ambiguous interpretations are drawn from the indirect pathway since it is potentially atherogenic to the extent that it may raise the plasma cholesteryl ester concentration in lipoproteins that are taken up by arterial wall macrophages. In addition, controversial roles are played in reverse cholesterol transport by LCAT and liver uptake of HDL-cholesteryl ester mediated by hepatic lipase (HL). HDL may exert several antiatherogenic effects unrelated to its role in cell cholesterol removal.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.