Isolation of subpopulations of high density lipoproteins: three particle species containing apoE and two species devoid of apoE that have affinity for heparin.

We have isolated and partially characterized five populations of lipoproteins from the pool of immunoisolated apoA-I-containing lipoproteins obtained from normal human plasma. The first three populations, each containing apoA-I and apoE, were isolated completely by sequential, selected affinity immunosorption against apoA-I and apoE. The lipoproteins isolated by this strategy fall into three morphologic groups; there are discs (LP-AI-E(1)), small spherical lipoproteins (LP-AI-E(2)), and large spherical lipoproteins (LP-AI-E(3)). The LP-AI-E(2) species was sufficiently abundant for detailed characterization. They have slightly larger diameters, and contain more lipid than the bulk of apoA-I-containing lipoproteins and they contain apoA-II:E heterodimers and apoE homodimers. Core lipids are enriched in triglyceride relative to cholesteryl esters. These lipoproteins compete with LDL equally, on a protein mass basis, for binding to human fibroblasts. After removal of apoE-containing lipoproteins from the pool of apoA-I-containing lipoproteins, we discovered two additional subpopulations of lipoproteins that bind to heparin. These lipoproteins, devoid of apoE, occur as populations of small, (LP-AI-HB(1)), and large, spherical lipoproteins, (LP-AI-HB(2). The heparin-binding lipoproteins were separated by gel permeation chromatography. The LP-AI-HB(1) population was of sufficient quantity for detailed study. These lipoproteins also had larger diameters than the bulk of HDL but their core lipids were enriched in cholesteryl esters rather than triglycerides. Three proteins associated with these lipoproteins were found to bind to heparin-Sepharose in the absence of lipid. The approximate molecular weights of these proteins are 40, 70, and 90 kDa. The 70 kDa molecule was found to be the SP 40,40 protein (apoJ).