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ABCG1's discovery as a large-HDL cholesterol exporter suggests CETP inhibition may enhance, not reduce, cholesterol efflux (Curr Opin Lipidol 2005)
Original title: High-density lipoproteins as therapeutic targets
This review of HDL as a therapeutic target highlights novel CETP inhibitors as HDL-raising agents showing extremely promising results, alongside the discovery that ATP-binding cassette transporter G1 (ABCG1) exports cellular cholesterol specifically to large HDL particles. That ABCG1 finding reconciles a prior inconsistency between basic research pointing to small, pre-beta-migrating HDL as the antiatherogenic fraction and epidemiological data implicating larger HDL particles as protective. Because CETP inhibition increases HDL particle size, the ABCG1 discovery provides circumstantial mechanistic evidence that CETP inhibition could enhance, rather than impair, cholesterol efflux and thereby inhibit atherosclerosis development, an argument in favor of the CETP inhibition strategy from an unexpected direction.
Original abstract
Purpose Of Review: The concentration of cholesterol in HDL is an inverse predictor of future cardiovascular disease, with evidence mounting that therapies that increase HDL concentration are antiatherogenic. The best known antiatherogenic function of HDL particles relates to their ability to promote the efflux of cholesterol from cells. However, they also have antioxidant, antiinflammatory and antithrombotic properties.
Recent Findings: The past year has seen the publication of several papers that highlight a potential major protective role of HDL in states of acute inflammation. Papers showing extremely promising results using novel inhibitors of cholesteryl ester transfer protein as HDL-raising agents have also appeared. Finally, the discovery that ATP-binding cassette transporter G1 (ABCG1) transports cell cholesterol to large HDL particles in the extracellular space has largely reconciled apparent inconsistencies between basic research indicating that small, pre-beta-migrating HDL particles are the antiatherogenic components of HDL and epidemiological research that implicates larger HDL particles as the protective fraction.
Summary: The finding that ABCG1 promotes the efflux of cholesterol from cells to large HDL particles also provides powerful circumstantial evidence that cholesteryl ester transfer protein inhibition (which increases HDL size) may enhance, rather than reduce, cholesterol efflux, and thus inhibit the development of atherosclerosis.
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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.