Formation of high density lipoprotein₂-like particles during lipolysis of very low density lipoproteins in vitro

The effects of lipolysis of human plasma very low density lipoprotein (VLDL) on the structure and composition of high density lipoproteins (HDL) have been investigated. Lipolysis was performed in a controlled system in vitro containing VLDL (d<1.006 g/ml) and HDL₃ (d=1.125-1.210 g/ml) from human plasma and lipoprotein lipase (EC 3.1.1.34) purified from bovine milk. Lipolysis of VLDL caused profound changes in HDL₃. Protein, phospholipid, and cholesterol liberated from VLDL during its lipolysis were transferred to the HDL₃ particles. As a consequence of this in vitro transfer, the chemical composition and biophysical properties of HDL₃ were substantially altered. The newly formed particles exhibited a flotation rate of 6.7 and a hydrated density of 1.110 g/ml. The chemical composition closely resembled that of native HDL₂, and their size was slightly larger than that of the precursor HDL₃. When HDL₃ and postlipolysis HDL₂ were subjected to ultracentrifugation under flotation velocity and equilibrium conditions, both proved to be stable particles. These results, when extrapolated to in vivo conditions, suggest an important metabolic relationship between the levels of circulating VLDL and HDL₂ in plasma. This relationship now permits a reasonable explanation for numerous in vivo observations in which the levels of VLDL and HDL₂ change reciprocally.