Isolation and characterization of two distinct species of human very low density lipoproteins lacking apolipoprotein E

We have isolated two fractions of very low density lipoprotein particles in human plasma that lack apolipoprotein (apo) E by combined anti-apoE and heparin affinity chromatography of whole plasma followed by ultracentrifugation. The two fractions are distinguished by their ability to bind to heparin. Each of these fractions, designated "B" particles to distinguish them from very low density lipoproteins that contain apoE ("B,E" particles), comprises an appreciable fraction of total particles in very low density lipoproteins of normolipidemic and hypertriglyceridemic subjects. The heparin-unbound B particles, which have been reported previously by others, are larger and have negligible affinity for low density lipoprotein receptors. The heparin-bound B particles are smaller and do bind to low density lipoprotein receptors, albeit with much lower affinity than B,E particles. No differences in accessibility to limited protease digestion were found between apoB-100 in the two types of B particles. Our data indicate that a substantial fraction of human very low density lipoproteins lacks apoE, the principal ligand for lipoprotein receptors that mediate the terminal catabolism of these lipoproteins. Whereas the B particles that fail to bind to heparin are likely to represent a form of nascent lipoprotein, the origin of those B particles that bind to heparin remains to be determined.