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A more recent version of this article appeared on August 1, 2006

Papers In Press, published online ahead of print May 10, 2006
J. Lipid Res., doi:10.1194/jlr.M600051-JLR200
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Submitted on January 31, 2006
Revised on April 13, 2006
Accepted on May 9, 2006

Absence of endogenous phospholipid transfer protein (PLTP) impairs ABCA1-dependent efflux of cholesterol from macrophage foam cells

Miriam Lee-Rueckert, Riikka Vikstedt, Jari Metso, Christian Ehnholm, Petri T. Kovanen, and Matti Jauhiainen

Wihuri Research Institute, Helsinki FIN-00140

Corresponding Author: petri.kovanen{at}wri.fi

In vitro experiments have demonstrated that exogenous phospholipid transfer protein (PLTP), i.e. purified PLTP added to macrophage cultures, influences ABCA1-mediated cholesterol efflux from macrophages to HDL. To investigate whether PLTP produced by the macrophages, i.e. endogenous PLTP, is also a part of this process we used peritoneal macrophages derived from PLTP-KO and WT mice. The macrophages were transformed to foam cells by cholesterol loading and this resulted in upregulation of ABCA1. Such macrophage foam cells from PLTP-KO mice released less cholesterol to lipid free apoA-I and to HDL than did the corresponding WT foam cells. Also, when plasma from either WT or PLTP-KO mice was used as an acceptor, cholesterol efflux from PLTP-KO foam cells was less efficient than that from WT foam cells. Treatment of foam cells with cAMP further upregulated the expression of ABCA1. Following cAMP treatment, cholesterol efflux from PLTP-KO foam cells to apoA-I increased markedly and reached to a level similar to that observed in cAMP-treated WT foam cells. Thus, the decreased cholesterol efflux observed in PLTP-KO foam cells could be restored to a level observed in WT foam cells. These results indicate that endogenous PLTP produced by macrophages is one component of the ABCA1-mediated cholesterol efflux-promoting machinery in these cells. Whether macrophage-PLTP acts at the plasma membrane or intracellularly needs further study.


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