Current concepts in reverse cholesterol transport

The term reverse cholesterol transport first introduced by Glomset (1), identifies a process where there is net flux of cholesterol from the peripheral tissues to the liver. Because the liver is the single organ capable of significant cholesterol elimination from the body via bile acids peripheral tissues must utilize this system for carrying excess cholesterol (both the newly synthesized and that derived from plasma) to the liver. Since the first inception of the idea it was held that circulating HDL were the plasma elements mainly implicated in reverse cholesterol transport. They would pick up cholesterol from extrahepatic cells through a process amplified by continous esterification of this cholesterol by lecithin cholesterol acyl transferase (LCAT), and final delivery to the liver. It has been within this conceptual framework that investigations on reverse cholesterol transport have developed in the last twenty years. The picture have become more complex with evidences for specific receptorial processes, protein(s) facilitating cholesteryl ester transfer between lipoproteins, and a number of other circulating putative tissue cholesterol acceptors/carriers in addition to HDL. The following is a brief account of the current status on reverse cholesterol transport research with some emphasis on the role of apolipoprotein A-IV (apoA-IV) which we have investigated more closely. The three main metabolic compartment composing the reverse cholesterol system, i.e. the peripheral tissue, the plasma compartment, and the liver, are discussed individually.