Plasma high density lipoproteins. Metabolism and relationship to atherogenesis.

Abstract

Introduction'Plasma HDL are small, dense, spherical lipid-protein com- plexes.They consist of -50% lipid and 50% protein.The major lipids are phospholipid (PL),2 cholesterol (C), choles- teryl esters (CE), and triglycerides (TG).The major proteins are apo A-I (Mr 28,000) and apo A-II (Mr 17,000).There are also a variety of minor but metabolically important apopro- teins in HDL called apo E and apo C (C-I, C-II, and C-Ill).HDL are heterogeneous and can be classified into larger, less dense HDL2 or smaller, denser HDL3.Although the major proportion of HDL is normally present in HDL3, individual variability in HDL levels in human populations usually re- flects different amounts of HDL2- A major known function of HDL is to act as a receptacle for excess PL and C, derived from cells or as by-products of lipolysis.These lipids are normally recycled from HDL to the liver in a process called reverse C transport (Fig. 1).This in- volves a direct pathway where C is transferred into HDL, then taken up by the liver, and also an indirect pathway, involving transfer of CE from HDL to VLDL, followed by uptake of VLDL in liver, or conversion of VLDL to LDL, and uptake of LDL by the liver.Another important function ofHDL is to act as a reservoir for apo E and C proteins.These proteins transfer onto TG-rich lipoproteins (e.g., during alimentary lipemia), providing a signal for the activation of lipolysis (the enzyme lipoprotein lipase [LPL] is activated by apo C-II) or targeting information that allows uptake of lipolyzed remnant lipoproteins by liver receptors (apo E is attracted to chylomicron or VLDL remnants and acts as a ligand for uptake of these parti- cles by liver receptors).