Triacylglycerol increase in plasma very low density lipoproteins in cyclophosphamide-treated rabbit: relationship with cholesteryl ester transfer activity.

We have studied the cholesteryl ester transfer between HDL and VLDL in cyclophosphamide-treated rabbits, in order to explain the abnormal cholesteryl ester partition between these two lipoprotein classes. The hypertriglyceridemia caused by treatment with the drug was associated with cholesteryl ester- and triacylglycerol-rich VLDL and with HDL poor in esterified cholesterol but relatively enriched in triacylglycerol. These two lipoprotein classes were characterized by their chemical composition and by gel filtration chromatography. VLDL particles were slightly larger in size, compared with controls. Different transfer combinations were envisaged between these abnormal lipoproteins and control ones. The transfer study involved the plasma fraction of d greater than 1.21 g/ml containing the cholesteryl ester transfer protein (CETP). It appeared that the chemical composition of lipoproteins was responsible for the level of cholesteryl ester transfer between lipoproteins. Actually, when the cholesteryl ester acceptor lipoproteins (VLDL) were enriched in triacylglycerol, the transfer was enhanced. Therefore, the effect of lipolysis on the transfer has also been explored. Lipoprotein lipase seemed to enhance the transfer of cholesteryl ester from HDL to VLDL when these lipoproteins were normal, but an important decline was obtained when triacylglycerol-rich VLDL were lipolyzed. This study defines the relationship between lipoprotein chemical composition and transfer activity of cholesteryl ester from HDL to VLDL.

Effects of an antimitotic agent (cyclophosphamide) on plasma lipoproteins.

A cyclophosphamide injection to male New Zealand white rabbits induced a pronounced hypertriglyceridemia and a hypercholesterolemia whose concentration was maximal at 16 hr. Different doses were studied. In this hyperlipemia significant changes in plasma lipoprotein fractions appeared: the very low density lipoproteins increased and the high density lipoproteins decreased. Lipid composition showed that HDL cholesterol was very low comparatively to a high VLDL cholesterol. The apoprotein composition of VLDL from treated rabbits was studied and compared to that of normal rabbits. After electrophoresis in urea/polyacrylamide gels, two new apoproteins which resembled those observed in irradiated rabbits appeared. The molecular weight of these proteins was about 10,000, and they focused into three bands with isoelectric points of 6.72, 6.42 and 6.10. Total lipoprotein lipase activity in treated rabbits decreased; it was very low with 32.5 mg/kg. This lipolytic activity remains to be studied after separation of hepatic triacylglycerol lipase and lipoprotein lipase activities by chromatography.