HDL begins as protein-rich discoidal structures, composed primarily of apoA-I, produced by the liver and intestines. Within the vasculature apoA-I interacts with the ATP-binding cassette transporter, ABCA1 (such as is diagrammed for interaction with macrophages) and extracts cholesterol from cells. Through the action of LCAT the apoA-I-associated cholesterol is esterified forming cholesterol esters. This process results in the generation of mature HDL particles. As the HDL particles continue through the circulation they pick up more cholesterol and through the action of LCAT, generate more cholesterol esters. As HDL migrates through the vasculature there is an interaction between them and IDL and LDL. This interaction occurs through the action of CETP which exchanges the cholesterol esters in the HDL for triglycerides from LDL. HDL can also remove cholesterol from cells via interaction with the ATP-binding cassette transporter ABCG1. Approximately 20% of HDL uptake of cellular cholesterol occurs via ABCG1. HDL cholesterol is then removed from the circulation by the liver through binding of the HDL to the hepatic HDL receptor, SR-B1 (see following paragraphs). Cholesterol ester-rich IDL and LDL can return to the liver and be taken up through interaction with the LDL receptor (LDLR). Within the vasculature the generation of reactive oxygen species (ROS) results in oxidation of lipid components of LDL generating oxidized LDL (oxLDL) which is taken up by macrophages via the scavenger receptor, FAT/CD36.
#hdlmetabolism #lipoprotein