Figure 1: Schematic diagram of HDL metabolic pathways and current drugs under development. Numbers in circles refer to Table 2. Pathway influencing HDL cholesterol metabolism, flux, and potential targets of therapeutic interventions. Both liver and intestine synthesize apolipoprotein A-I (ApoA-I) secreted as lipid-poor particles. These particles are lipidated with phospholipids and cholesterol via the hepatocyte ATP-binding cassette A1 (ABCA1) transporter to form nascent HDL. In peripheral tissues these HDL particles obtain free cholesterol via the macrophage ABCA1 and ABCG1 transporters, which are regulated by LXRs and miR-33. Free cholesterol transferred via ABCA1 and ABCG1 onto HDL is esterified by lecithin: cholesterol acyltransferase (LCAT) to form cholesteryl esters (CE). Mature HDL thus formed exchange CE trough cholesteryl ester transfer protein (CETP) onto apoB-containing lipoproteins, (VLDL and LDL) with subsequent uptake in the liver via the low-density lipoprotein receptor (LDLR). PLTP mediates transfer of phospholipid from triglyceride from VLDL into HDL, which promote HDL remodeling. The resulting HDL3 particles can be either taken up by the liver via SB-B1 or modified by hepatic lipase (HL) and endothelial lipase (EL), which hydrolyze HDL phospholipids and triglycerides. Metabolism by EL releases lipid-poor apoA-I, which can be catabolized in kidney. Targets of HDL-directed therapeutic interventions are indicated by red arrow.