Modifications of plasma lipoproteins after lipase activation in patients with chylomicronemia

Lipoprotein lipase (LPL) and hepatic lipase (HL) are enzymatic activities involved in lipoprotein metabolism. The purpose of this study was to analyze the physicochemical modifications of plasma lipoproteins produced by LPL activation in two patients with apoC-II deficiency syndrome and by HL activation in two patients with LPL deficiency. LPL activation was achieved by the infusion of normal plasma containing apoC-II and HL was released by the injection of heparin. Lipoproteins were analyzed by ultracentrifugation in a zonal rotor under rate flotation conditions before and after lipase activation. The LPL activation resulted in: a reduction of plasma triglycerides; a reduction of fast-floating very low density lipoprotein (VLDL) concentration; an increase of intermediate density lipoprotein (IDL), which maintained unaltered flotation properties; an increase of low density lipoproteins (LDL) accompanied by modifications of their flotation rates and composition; no significant variations of high density lipoprotein (HDL) levels; and an increase of the HDL flotation rate. The HL activation resulted in: a slight reduction of plasma triglycerides; a reduction of the relative triglyceride content of slow-floating VLDL, IDL, LDL2, and HDL3 accompanied by an increase of phospholipid in VLDL and by an increase of cholesteryl ester in IDL; and a reduction of the HDL flotation rate. These experiments in chylomicronemic patients provide in vivo evidence that LPL and HL are responsible for plasma triglyceride hydrolysis of different lipoproteins, and that LPL is particularly involved in determining the levels and physicochemical properties of LDL. Moreover, in these patients, the LPL activation does not directly change the HDL levels, and LPL or HL does not produce a step-wise conversion of HDL3 to HDL2 (or vice versa) but rather modifies the flotation rates of all the HDL molecules present in plasma.