Phospholipid Transfer Protein Mediates Transfer of not Only Phosphatidylcholine but Also Cholesterol from Phosphatidylcholine-Cholesterol Vesicles to High Density Lipoproteins

Abstract

Phospholipid transfer protein (PLTP) purified from human plasma was found to enhance the transfer of cholesterol from single bilayer vesicles containing phosphatidylcholine and cholesterol to high density lipoprotein-3. The rate of cholesterol transfer was greatly influenced by the cholesterol content of the donor vesicles. The maximal rate was observed with the vesicles containing 20 -25 mol % cholesterol. This was in contrast to a progressive decline in the rate of phosphatidylcholine transfer with an increase in the cholesterol content. To determine the binding of cholesterol and phosphatidylcholine to PLTP, the mixtures of PLTP and the vesicles containing 3 H-labeled phosphatidylcholine and 14 C-labeled cholesterol were incubated and subjected to sucrose density gradient centrifugation. Determination of the label profiles showed that cholesterol as well as phosphatidylcholine were transferred from the vesicles to PLTP. The reversible nature of the binding was shown by the transfer of labeled cholesterol and phosphatidylcholine bound to PLTP to the acceptor vesicles or low density lipoprotein. Isothermal equilibrium binding of PLTP for cholesterol and phosphatidylcholine showed that PLTP possessed a considerably higher affinity and binding capacity for phosphatidylcholine than for cholesterol. The phosphatidylcholine binding affinity and capacity were greater when PLTP was incubated with phosphatidylcholine vesicles without cholesterol. A possible importance of PLTP-mediated cholesterol transfer in the circulation was described.

Human Plasma Phospholipid Transfer Protein Increases the Antiatherogenic Potential of High Density Lipoproteins in Transgenic Mice

“…In addition to the proposed mechanism of action of PLTP on cellular cholesterol efflux via the generation of pre-␤-HDL, PLTP could also contribute directly to cellular cholesterol efflux via its proposed cholesterol transfer activity. 37 Plasma levels of total HDL cholesterol are inversely correlated with the incidence of coronary artery disease in humans. 7,8 However, only a few studies have looked at the relation between total HDL and pre-␤-HDL in human plasma.…”

Active plasma phospholipid transfer protein is associated with apoA-I- but not apoE-containing lipoproteins

“…It can facilitate the transfer of surface lipids from triglyceride-rich lipoproteins to HDL during lipolysis (1)(2)(3) and can convert HDL into larger and smaller particles, generating preb HDL in the process (4,5). PLTP also interacts with the ATP binding cassette transporter A1 and enhances lipid efflux from cells (6,7).…”

Dry Eye Symptoms Are Increased in Mice Deficient in Phospholipid Transfer Protein (PLTP)

“…This is in line with the proposed pleiotropic effects of PLTP in plasma, 37 as well as with the very high lipid binding and transfer potential of PLTP. 36 We believe that the mouse PLTP KO model serves as a relevant model of human DES. The specific mechanism of PLTP in lipid transfer processes in tear, detailed lipid composition of tear fluid, and possible alterations in PLTP activity in DES patients will be important targets to investigate in more detail to define the exact role of PLTP in DES.…”

“…Here, PLTP can remove the harmful overload of lipids and other lipophilic substances and transfer these to the lacrimal drainage system. It needs to be emphasized that PLTP can maximally bind and transfer 43 and 13 moles of phosphatidylcholine and cholesterol, respectively, per mole of PLTP, 36 allowing for a very efficient lipid transfer activity. This mode of action is very similar to the one described for human tear lipocalin.…”