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 Dec 1
Externally publishedYes

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Keywords

  • Atherosclerosis
  • Cholesterol
  • Lipids
  • Lipoproteins
  • Oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

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