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Cholesterol efflux from macrophage foam cells is enhanced by active phospholipid transfer protein through generation of two types of acceptor particles.

Abstract：

:Phospholipid transfer protein (PLTP) is expressed by macrophage-derived foam cells in human atherosclerotic lesions, suggesting a regulatory role for PLTP in cellular cholesterol homeostasis. However, the exact role of PLTP in the reverse cholesterol transport pathway is not known. PLTP is present in plasma as two forms, a highly active (HA-PLTP) and a lowly active (LA-PLTP) form. In this study we clarify the role of the two forms of PLTP in cholesterol efflux from [3H]cholesterol oleate-acetyl-LDL-loaded THP-1 macrophages. Incubation of HDL in the presence of HA-PLTP resulted in the formation of two types of acceptor particles, prebeta-HDL and large fused HDL. HA-PLTP increased prebeta-HDL formation and caused a 42% increase in [3H]cholesterol efflux to HDL, while LA-PLTP neither formed prebeta-HDL nor increased cholesterol efflux. Removal of the formed prebeta-HDL by immunoprecipitation decreased cholesterol efflux by 47%. Neither HA- nor LA-PLTP enhanced cholesterol efflux to lipid-free apoA-I. Importantly, also the large fused HDL particles formed during incubation of HDL with HA-PLTP acted as efficient cholesterol acceptors. These observations demonstrate that only HA-PLTP increases macrophage cholesterol efflux, via formation of efficient cholesterol acceptors, prebeta-HDL and large fused HDL particles.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Vikstedt R,Metso J,Hakala J,Olkkonen VM,Ehnholm C,Jauhiainen M

doi

10.1021/bi700833h

subject

Has Abstract

pub_date

2007-10-23 00:00:00

pages

11979-86

issue

42

eissn

0006-2960

issn

1520-4995

journal_volume

46

pub_type

杂志文章

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