DISSOCIATION OF LPL AND LDL - EFFECTS OF LIPOPROTEINS AND ANTI-APO-B ANTIBODIES

We have shown previously that the activity of lipoprotein lipase (LPL) , the major enzyme responsible for hydrolysis of triglyceride containe d in circulating lipoproteins, is associated with lipoproteins in post heparin plasma. In other studies, microtiter plate assays showed that LPL interaction with low density lipoprotein (LDL) and very low densit y lipoprotein (VLDL) was decreased by antibodies to apolipoprotein (ap o)B. To test whether antibodies to apoB affected LPL-LDL association i n solution, two types of assays were performed, gel filtration and cop recipitation. First we showed that LPL activity and immunoreactive mas s co-eluted during gel filtration of normal postheparin plasma, approx imately with the peak of low density lipoproteins. Then LPL was used f or gel filtration studies in the presence and absence of LDL and anti- apoB monoclonal antibodies. LPL association with LDL was diminished by antibodies to the amino-terminal region of apoB; antibodies to the ca rboxyl-terminal LDL receptor binding region of apoB were less effectiv e. LDL binding to LPL containing heparin-agarose was also disrupted by the amino-terminal antibodies to apoB. To determine the LPL-lipoprote in association in situations in which the distribution of plasma lipop roteins was altered, we studied plasma from two types of subjects with dyslipidemias. The addition of I-125-labeled LPL to type 1 posthepari n plasma produced two peaks of radioactivity, one peak eluted in the v oid volume of the column (with the chylomicrons) and a second peak elu ted just prior to the normal elution of low density lipoproteins. In p ostheparin plasma from an abetalipoproteinemic subject, LPL eluted wit h HDL. We conclude that LPL associates primarily with apoB-containing lipoproteins. The reason for this appears to be that LPL interacts wit h the apoB.