Regulation of lipid transfer between lipoproteins by an endogenous plasma protein: selective inhibition among lipoprotein classes.

R E Morton,D J Greene

doi:10.1016/s0022-2275(20)39178-1

Abstract

Lipid transfer protein (LTP) remodels plasma lipoproteins by promoting mass transfers of cholesteryl ester (CE) and triglyceride between lipoproteins. We have investigated the capacity of an additional plasma protein, lipid transfer inhibitor protein (LTIP) to modify the functional activity of LTP in a complex mixture of lipoproteins. Transfer assays containing isolated LTP, LTIP, and the three major lipoprotein classes, and assays with intact human plasma supplemented with exogenous LTIP were used. In both assays, the inhibition of CE transfer by LTIP varied markedly depending on the lipoproteins involved and was dependent on LTIP concentration. Inhibition of lipid transfer between a given pair of lipoproteins was similar. However, between lipoprotein pairs the extent of inhibition was very different, varying up to 7-fold. Inhibition followed the order of very low density lipoprotein (VLDL)-low density lipoprotein (LDL) transfers > LDL-high density lipoprotein (HDL) transfers > VLDL-HDL transfers. Consistent with the preferential inhibition of transfer events involving LDL, LTIP was shown by gel filtration studies to associate primarily with LDL in plasma. The addition of LTIP to native plasma stimulated the LTP-mediated efflux of CE from HDL to VLDL; this occurred at the expense of LDL CE depletion. Thus, LTIP alters the pattern of lipid transfer reactions in plasma by uniquely affecting the individual transfer events mediated by LTP. By preferentially diminishing transfer events involving LDL, especially those between VLDL and LDL, LTIP enhances the ability of LTP to remove CE from HDL, and thus alters HDL metabolism.

Highlights

Lipid transfer protein (LTP) remodels plasma lipoproteins by promoting mass transfers of cholesteryl ester (CE) and triglyceride between lipoproteins
Utilizing immobilized lipoproteins as a binding site for LTP, we demonstrated that lipid transfer inhibitor protein (LTIP) binds to lipoproteins and that LTIP can prevent LTP binding when it is added to lipoproteins first, or it can disrupt preexisting LTP-lipoprotein complexes when added after the transfer protein is bound [17]
By molecular weight and isoelectric point criteria [14,15,16], LTIP appears to be unique among the plasma proteins that have been previously characterized as having an affinity for lipoproteins [43]

Summary

Introduction

Lipid transfer protein (LTP) remodels plasma lipoproteins by promoting mass transfers of cholesteryl ester (CE) and triglyceride between lipoproteins. Transfer assays containing isolated LTP, LTIP, and the three major lipoprotein classes, and assays with intact human plasma supplemented with exogenous LTIP were used In both assays, the inhibition of CE transfer by LTIP varied markedly depending on the lipoproteins involved and was dependent on LTIP concentration. Consistent with the preferential inhibition of transfer events involving LDL, LTIP was shown by gel filtration studies to associate primarily with LDL in plasma. By preferentially diminishing transfer events involving LDL, especially those between VLDL and LDL, LTIP enhances the ability of LTP to remove CE from HDL, and alters HDL metabolism.-Morton, R. T h e level of LTP activity in both humans and laboratory animals has been shown to vary remarkably under both normal and hyperlipidemic conditions. Subsequent reports by Son and Zilversmit [15] and by Nishide, Tollefson, and Albers [16] have confirmed and

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