ABNORMAL ACTIVATION OF LIPOPROTEIN-LIPASE BY NON-EQUILIBRATING APOC-II - FURTHER EVIDENCE FOR THE PRESENCE OF NON-EQUILIBRATING POOLS OF APOLIPOPROTEINS C-II AND C-III IN PLASMA-LIPOPROTEINS

Using artificial triglyceride emulsions, we have demonstrated the pres ence of non-equilibrating pools of apolipoproteins C-II and C-III in h uman plasma lipoproteins. As the concentrations of acceptor triglyceri des were increased, a greater fraction of both apoC-II and apoC-III sh ifted away from the native plasma lipoproteins to the artificial lipid emulsions. All of the apoC-II and apoC-III in very low density and hi gh density lipoproteins (VLDL and HDL), however, could not be removed from native plasma lipoproteins. The percent of total plasma apoC-II a nd apoC-III that could be recovered in the VLDL and HDL density fracti ons varied when plasma from different individuals was used. When plasm a samples from normotriglyceridemic subjects were used, HDL was the pr imary donor of apoCs. The percent of total plasma apoCs associated wit h HDL decreased from 60% to 25% for apoC-II and from 65% to 15% for ap oC-III. When plasma samples from hypertriglyceridemic subjects were in cubated with artificial lipid emulsions, VLDL was the primary donor of apoCs. HDL from hypertriglyceridemic subjects only accounted for 5-10 % of total fasting plasma apoCs and did not contribute significantly t o the final apoC contents of the artificial triglyceride emulsions. To evaluate the significance of the depletion of exchangeable apoCs from plasma HDL, we also examined the ability of control and apoC-depleted HDL to serve as activator for bovine milk lipoprotein lipase (LPL) in vitro. When HDL depleted of exchangeable apoCs were used as the sourc e of plasma apolipoproteins for the activation of LPL in vitro, only 5 -10% of the maximal activity obtained with native HDL was demonstrated . In fact, in the presence of comparable concentrations of HDL apoC-II , activation of LPL was the least with HDL which lacked exchangeable a poCs. Our data thus indicated that the presence of exchangeable apoC-I I on HDL is necessary for the activation of LPL in vitro. This finding is consistent with our data that suggest that HDL from hypertriglycer idemic subjects do not stimulate LPL as well as HDL from normolipidemi c subjects.