High-density lipoprotein and atherosclerosis: Roles of lipid transporters

Abstract

Various previous studies have found a negative correlation between the risk of cardiovascular events and serum high-density lipoprotein (HDL) cholesterol levels. The reverse cholesterol transport, a pathway of cholesterol from peripheral tissue to liver which has several potent antiatherogenic properties. For instance, the particles of HDL mediate to transport cholesterol from cells in arterial tissues, particularly from atherosclerotic plaques, to the liver. Both ATP-binding cassette transporters (ABC) A1 and ABCG1 are membrane cholesterol transporters and have been implicated in mediating cholesterol effluxes from cells in the presence of HDL and apolipoprotein A-I, a major protein constituent of HDL. Previous studies demonstrated that ABCA1 and ABCG1 or the interaction between ABCA1 and ABCG1 exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing HDL cholesterol levels as well as enhancing HDL biochemical functions. HDL therapies that use injections of reconstituted HDL, apoA-I mimetics, or full-length apoA-I have shown dramatic effectiveness. In particular, a novel apoA-I mimetic peptide, Fukuoka University ApoA-I Mimetic Peptide, effectively removes cholesterol via specific ABCA1 and other transporters, such as ABCG1, and has an antiatherosclerotic effect by enhancing the biological functions of HDL without changing circulating HDL cholesterol levels. Thus, HDL-targeting therapy has significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a therapeutic tool for atherosclerotic cardiovascular diseases.

Keywords: ATP-binding cassette transporter; ATP-binding cassette A1; ATP-binding cassette G1; Apolipoprotein A-I; High-density lipoprotein; High-density lipoprotein therapy; apoA-I mimetic peptide; Reconstitutedf high-density lipoprotein

Core tip: The reverse cholesterol transport pathway played with high-density lipoprotein (HDL) has several potential antiatherogenic properties. Both ATP-binding cassette (ABC) A1 and ABCG1 are lipid transporters and have been involved in mediating cholesterol effluxes from cells in the presence of HDL or apoA-I, and they exerted antiatherosclerotic effects. As a therapeutic approach for increasing HDL cholesterol levels, much focus has been placed on increasing not only HDL cholesterol levels, but also HDL-biological functions. Reconstituted HDL and apoA-I mimetics have significant atheroprotective potential, as it uses lipid transporter-targeting agents, and may prove to be a novel therapeutic tool for atherosclerotic cardiovascular diseases.