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 less than 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 (F01.20) 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.