J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M800174-JLR200 on July 3, 2008 Originally published In Press as doi:10.1194/jlr.M800174-JLR200 on July 1, 2008

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Journal of Lipid Research, Vol. 49, 2230-2239, October 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma

Claes Bergmark*, Asheesh Dewan{dagger}, Alexina Orsoni§, Esther Merki{dagger}, Elizabeth R. Miller{dagger}, Min-Jeong Shin**, Christoph J. Binder{dagger},§§, Sohvi Hörkkö{dagger}, Ronald M. Krauss{dagger}{dagger}, M. John Chapman§, Joseph L. Witztum{dagger} and Sotirios Tsimikas1,{dagger}

* From the Department of Vascular Surgery, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden
{dagger} Department of Medicine, University of California at San Diego, La Jolla, CA
§ Dyslipidemia and Atherosclerosis Research Unit, Institut national de la santé et de la recherche médicale, Unit 551, Université Pierre et Marie Curie, Paris 6, Cedex 13
** Yonsei Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea
{dagger}{dagger} Children's Hospital Oakland Research Institute, Oakland, CA
§§ Medical University of Vienna, Vienna, Austria

This study was supported by grants HL56989 (La Jolla Specialized Center of Research in Molecular Medicine and Atherosclerosis), HL69646, HL57505, the Donald W. Reynolds Foundation, the Fondation Leducq, and the Throne-Holst Foundation. These studies were carried out in part in the General Clinical Research Center, University of California, San Diego with funding provided by the National Center for Research Resources, M01RR00827, United States Public Health Service.

Published, JLR Papers in Press, July 3, 2008.

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

Oxidized phospholipids (OxPLs) on apolipoprotein B-100 (apoB-100) particles are strongly associated with lipoprotein [a] (Lp[a]). In this study, we evaluated whether Lp[a] is preferentially the carrier of OxPL in human plasma. The content of OxPL on apoB-100 particles was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPLs were preferentially bound by Lp[a] as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies, and chemiluminescent ELISAs were performed. Immunoprecipitation of Lp[a] from human plasma with an apolipoprotein [a] (apo[a])-specific antibody demonstrated that more than 85% of E06 reactivity (i.e., OxPL) coimmunoprecipitated with Lp[a]. Ultracentrifugation experiments showed that nearly all OxPLs were found in fractions containing apo[a], as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPLs to Lp[a], as opposed to LDL, in a time- and temperature-dependent manner, even in aqueous buffer. Approximately 50% of E06 immunoreactivity could be extracted from isolated Lp[a] following exposure of plasma to various lipid solvents. These data demonstrate that Lp[a] is the preferential carrier of PC-containing OxPL in human plasma. This unique property of Lp[a] suggests novel insights into its physiological function and mechanisms of atherogenicity.

Supplementary key words lipoproteins • atherosclerosis • lipids • cholesterol • oxidation

Abbreviations: apo[a], apolipoprotein [a]; CAD, coronary artery disease; CVD, cardiovascular disease; Lp[a], lipoprotein [a]; MDA, malondialdehyde; OxLDL, oxidized LDL; OxPL, oxidized phospholipid; OxPL/apoB, oxidized phospholipid epitopes per apolipoprotein B-100; PC, phosphocholine; PCI, percutaneous coronary intervention; RLU, relative light unit


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