Targeting high-density lipoproteins: update on a promising therapy

Abstract

Numerous epidemiological studies have demonstrated the atheroprotective roles of high density lipoproteins (HDL), so that HDL is established as an independent negative risk factor. The protective effect of HDL against atherosclerosis is mainly attributed to their capacity to bring peripheral excess cholesterol back to the liver for further elimination into the bile. In addition, HDL can exert other protective functions on the vascular wall, through their anti-inflammatory, antioxidant, antithrombotic and cytoprotective properties. HDL-targeted therapy is thus an innovative approach against cardiovascular risk and atherosclerosis. These pleiotropic atheroprotective properties of HDL have led experts to believe that "HDL-related therapies" represent the most promising next step in fighting against atherosclerosis. However, because of the heterogeneity of HDL functions, targeting HDL is not a simple task and HDL therapies that lower cardiovascular risk are NOT yet available. In this paper, an overview is presented about the therapeutic strategies currently under consideration to raise HDL levels and/or functions. Recently, clinical trials of drugs targeting HDL-C levels have disappointingly failed, suggesting that HDL functions through specific mechanisms should be targeted rather than increasing per se HDL levels.

Keywords: ABCA1; ABCG1; ATP; Acide nicotinique; Adenosine triphosphate; Adenosine triphosphate binding cassette A1; Adenosine triphosphate binding cassette G1; ApoA-I transcription; Apolipoprotein; CETP; CETP inhibitor; CVD; Cardiovascular disease; Cholesteryl ester transfer protein; HDL; HDL-C; HDL-therapy; HDL-thérapie; High-density lipoprotein; High-density lipoprotein cholesterol; Inhibiteurs de CETP; LCAT; LDL; LDL-C; LXR; Lecithin cholesterol acyl transferase; Liver X receptor; Low-density lipoprotein; Low-density lipoprotein cholesterol; Mimetic peptides; Niacin; P2Y(13); PPAR; Peptides mimétiques; Peroxisome proliferator-activated receptor; Purinergic receptor 13; RCT; Reverse cholesterol transport; Régulation transcriptionnelle de l’apo A-I; SR-BI; Scavenger receptor class B type I; VLDL; Very-low-density lipoprotein; apo.