DIMERIC LIPOPROTEIN LIPASE ACTIVITY IS BOUND TO TRIGLYCERIDE-RICH LIPOPROTEINS IN POSTHEPARIN PLASMA

Lipoprotein lipase hydrolyzes the triglyceride-rich core of chylomicrons and very low density lipoproteins. It is also a ligand, in vitro, for binding of lipoproteins to the low density lipoprotein receptor-related protein and may play a central role in the receptor-mediated removal of triglyceride-rich lipoproteins. The aim of the present study was to determine to which lipoprotein subclass the enzyme is bound in preheparin plasma and when released into plasma by heparin injection. Tetrahydrolipstatin, a potent inhibitor of serine lipases, was used to block lipolytic activity, thereby preventing changes in plasma lipoproteins due to ex vivo lipolysis. To analyze the distribution pattern of lipoprotein lipase dimers among lipoprotein classes, a specific ELISA was used and gel filtration was performed in pre- and postheparin plasma from five subjects with triglyceride ranging from 69 to 522 mg/dl. When lipolytic activity was not inhibited, lipoprotein lipase dimers eluted in association with low and high density lipoproteins, reproducing results previously obtained by several groups of investigators. However, in pre- and postheparin samples treated with tetrahydrolipstatin, most of the dimeric enzyme was found associated with very low density lipoprotein particles. In conclusion in pre- and postheparin samples most of the lipoprotein lipase dimers are associated with very low density lipoproteins when ex vivo lipolytic activity is inhibited, which supports the hypothesis that, in vivo, lipoprotein lipase may affect the receptor-mediated removal of these particles. Moreover, it suggests that the association between lipoprotein lipase and cholesterol-rich lipoproteins might be an ex vivo phenomenon due to lack of inhibition of lipolytic activity.