Figure 3: Metabolic pathway of high-density lipoprotein and sites of therapeutic intervention. The formation of nascent high-density lipoprotein molecules begins with apolipoprotein A-I (apoA-I) synthesis in the liver. ApoA-I expression stimulators increase apoA-I synthesis while apoA-I mimetic peptides provide a synthetic surrogate. These apoA-1 molecules and infusible HDL mimetics can then receive cholesterol and phospholipids from macrophages via ATP-binding membrane cassette (ABC) transporter-mediated efflux. The liver X receptor (LXR) agonists, farnesoid X receptor (FXR) agonists, and peroxisome proliferator-activated receptor (PPAR) agonists can upregulate this lipid efflux process by increasing expression of ABC transporters. Inhibition of cholesteryl ester transfer from the resulting HDL3 (smaller, more dense particles) and HDL2 (larger, less dense particles) via cholesteryl ester transfer protein (CETP) can be blocked by CETP inhibitors. Inhibition of HDL cholesterol uptake by the liver and macrophages via scavenger receptor BI (SR-BI) inhibitors can also lead to elevated HDL cholesterol levels. Abbreviations: ABCA1, ATP binding membrane cassette transporter A1; ABCG1, ATP binding membrane cassette transporter G1; ABCG4, ATP binding membrane cassette transporter G4; ApoA-I, apolipoprotein A-I; CETP, cholesteryl ester transfer protein; FXR, farnesoid X receptor; HDL, high-density lipoprotein; LXR, liver X receptor; PPAR, peroxisome proliferator-activated receptor; SR-B1, scavenger receptor B1.