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Journal of Lipid Research, Vol. 45, 1852-1858, October 2004
Copyright © 2004 by American Society for Biochemistry and Molecular Biology

PLTP deficiency improves the anti-inflammatory properties of HDL and reduces the ability of LDL to induce monocyte chemotactic activity

Daoguang Yan^*, Mohamad Navab, Can Bruce^*, Alan M. Fogelman and Xian-Cheng Jiang^1,*

^* Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY 10032
UCLA School of Medicine, Los Angeles, CA 90095

¹ To whom correspondence should be addressed. e-mail: xjiang{at}downstate.edu

We reported that phospholipid transfer protein (PLTP) deficiency decreased atherosclerosis in mouse models. Because the decreased atherosclerosis was accompanied by a significant decrease in plasma HDL levels, we examined the properties of PLTP knockout (PLTP0) HDL and tested its ability to prevent LDL-induced monocyte chemotactic activity in human artery wall cell cocultures. We isolated HDL and LDL from LDL receptor knockout/PLTP knockout (LDLr0/PLTP0) mice and from apolipoprotein B transgenic (apoBTg)/PLTP0 mice as well as their controls. PLTP0 HDL was relatively rich in protein and depleted in phosphatidylcholine. Turnover studies revealed a 3.5- to 4.0-fold increase in the turnover of protein and cholesteryl ester in HDL from PLTP0 mice compared with control mice. The ability of HDL from LDLr0/PLTP0 and apoBTg/PLTP0 mice to prevent the induction of monocyte chemotactic activity in human artery wall cell cocultures exposed to human LDL was dramatically better than that in controls. Moreover, LDL from PLTP0 mice was markedly resistant to oxidation and induced significantly less monocyte chemotactic activity compared with that in controls. In vitro, PLTP0 HDL removed significantly more oxidized phospholipids from LDL than did control HDL.

We conclude that PLTP deficiency improves the anti-inflammatory properties of HDL in mice and reduces the ability of LDL to induce monocyte chemotactic activity.

Abbreviations: apoB, apolipoprotein B; BLp, apolipoprotein B-containing lipoprotein; CE, cholesteryl ester; FCR, fractional catabolic rate; FPLC, fast-protein liquid chromatography; LDLr0, LDL receptor knockout; PC, phosphatidylcholine; PLTP, phospholipid transfer protein; PLTP0, phospholipid transfer protein knockout; SM, sphingomyelin; Tg, transgenic; WT, wild-type

Supplementary key words high density lipoprotein • low density lipoprotein • phospholipid transfer protein • phospholipid

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