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

Claes Bergmark, Asheesh Dewan, Alexina Orsoni, Esther Merki, Elizabeth R. Miller, Min Jeong Shin, Christoph J. Binder, Sohvi Hörkkö, Ronald M. Krauss, M. John Chapman, Joseph L. Witztum, Sotirios Tsimikas

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Abstract

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.

Original languageEnglish
Pages (from-to)2230-2239
Number of pages10
JournalJournal of Lipid Research
Volume49
Issue number10
DOIs
Publication statusPublished - 2008

Keywords

  • Atherosclerosis
  • Cholesterol
  • Lipids
  • Lipoproteins
  • Oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Bergmark, C., Dewan, A., Orsoni, A., Merki, E., Miller, E. R., Shin, M. J., Binder, C. J., Hörkkö, S., Krauss, R. M., Chapman, M. J., Witztum, J. L., & Tsimikas, S. (2008). A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. Journal of Lipid Research, 49(10), 2230-2239. https://doi.org/10.1194/jlr.M800174-JLR200