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 Hörkö, Ronald M. Krauss, M. John Chapman, Joseph L. Witztum, and Sotirios Tsimikas

Medicine/Cardiology, University of California San Diego, La Jolla, CA 92093-0682

Corresponding Author: stsimikas{at}ucsd.edu

Objectives Oxidized phospholipids (OxPL) on apolipoprotein B-100 particles are strongly associated with lipoprotein (a) [Lp(a)]. In this study, we evaluated whether Lp(a) is the preferentially carrier of OxPL in human plasma. Methods and Results The content of OxPL on apolipoprotein B-100 particles (OxPL/apoB) was measured with monoclonal antibody E06, which recognizes the phosphocholine (PC) headgroup of oxidized but not native phospholipids. To assess whether OxPL were preferentially bound by Lp(a) as opposed to other lipoproteins, immunoprecipitation and ultracentrifugation experiments, in vitro transfer studies and chemiluminescent enzyme linked immunosorbent assays were performed. Immunoprecipitation of Lp(a) from human plasma with an apolipoprotein(a)-specific antibody demonstrated that more than 85% of E06 reactivity (i.e. OxPL) co-immunoprecipitated with Lp(a). Ultracentrifugation experiments showed that nearly all OxPL were found in fractions containing apolipoprotein(a), as opposed to other apolipoproteins. In vitro transfer studies showed that oxidized LDL preferentially donates OxPL 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. Conclusions 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.

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