Hugh sinclair lecture: the regulation and remodelling of HDL by plasma factors.
High density lipoproteins (HDLs) originate as lipid-free or lipid-poor apolipoproteins that acquire most of their lipid in the extracellular space. They accept phospholipids from cells in a process promoted by the ATP binding cassette A1 transporter to form prebeta-migrating discoidal HDL that are efficient acceptors of cholesterol released from cell membranes. The cholesterol in discoidal HDL is esterified by lecithin:cholesterol acyltransferase (LCAT) in a process that converts the prebeta-migrating disc into an alpha-migrating, spherical HDL. Spherical HDL are further remodelled by cholesteryl ester transfer protein (CETP) that transfers cholesteryl esters from HDL to other lipoproteins and by hepatic lipase that hydrolyses HDL triglyceride in processes that reduce HDL size and lead to the dissociation of prebeta-migrating, lipid-poor apolipoprotein (apo)A-I from the particle. Prebeta-migrating, lipid-poor apoA-I is also generated as a product of the remodelling of HDL by phospholipid transfer protein. Thus, apoA-I cycles between lipid-poor and lipid associated forms as part of a highly dynamic metabolism of HDL. The other main HDL apolipoprotein, apoA-II is incorporated into apoA-I-containing particles in a process of particle fusion mediated by LCAT. Extracellular assembly and remodelling of HDL not only plays a major role in HDL regulation but also provides potential targets for therapeutic intervention. One example of this is the development of inhibitors of CETP.
Barter
P J
PJ
Hanson Institute, Adelaide, SA, Australia. pbarter@medicine.adelaide.edu.au
D016632:Apolipoprotein A-I / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D001161:Arteriosclerosis / Q000473:pathology* / Q000503:physiopathology*; D001798:Blood Proteins / Q000494:pharmacology*; D006801:Humans; D008075:Lipoproteins, HDL / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure*
D016632:Apolipoprotein A-I; D001798:Blood Proteins; D008075:Lipoproteins, HDL