Reverse cholesterol transport

ApoA-I is produced by the liver and acquires free cholesterol and phospholipid from liver and peripheral cells (including macrophages) via the ATP-binding cassette transporter A1 (ABCA1) to form nascent (discoidal) HDL particles. Nonlipidated apoA-I is cleared by the kidney. Free cholesterol efflux from macrophages to HDL particles is also promoted by the ABCG1 transporter and scavenger receptor class B type 1 (SR-BI). The free cholesterol in discoidal HDL particles is converted to cholesteryl ester by lecithin-cholesterol acyltransferase (LCAT) activity leading to the formation of mature, spherical HDL particles. Phospholipid transfer protein (PLTP) mediates transfer of phospholipids from VLDL into HDL, thereby providing phospholipids for the LCAT reaction. Mature HDL particles can be remodeled to smaller particles with the release of apoA-I by the actions of hepatic lipase and endothelial lipase, which hydrolyze HDL triglycerides and phospholipids, respectively. In humans, but not rodents, HDL cholesterol ester can be transferred to the VLDL/LDL pool by cholesteryl ester transfer protein (CETP) and taken up by endocytosis into hepatocytes via interaction with the LDL receptor (LDLR). HDL cholesterol ester and free cholesterol are also transferred directly to hepatocytes via SR-BI-mediated selective uptake. Cholesterol taken up by the liver can be recycled back into the ABCA1 pathway, secreted into bile as either free cholesterol or bile acids, or assembled into lipoprotein particles that are secreted back into the circulation (not shown).