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Papers In Press, published online ahead of print September 1, 2009
J. Lipid Res., doi:10.1194/jlr.M800342-JLR200

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Journal of Lipid Research, Vol. 50, 1735-1743, September 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Relationship of lipoprotein-associated phospholipase A₂ and oxidized low density lipoprotein in carotid atherosclerosis^[S]

Kasey C. Vickers^*, Colin T. Maguire^*, Robert Wolfert, Alan R. Burns^*, Michael Reardon, Richard Geis, Paul Holvoet^** and Joel D. Morrisett^1,*,

^* Department of Medicine, Baylor College of Medicine, Houston, TX
Department of Biochemistry/Molecular Biology, Baylor College of Medicine, Houston, TX
diaDexus Inc., South San Francisco, CA
Department of Surgery, Methodist Hospital, Houston, TX
^** Department of Cardiovascular Diseases, Katholieke Universiteit, Leuven, Belgium

¹ To whom correspondence should be addressed. e-mail: morriset{at}bcm.tmc.edu

Plasma levels of lipoprotein-associated phospholipase A₂ (Lp-PLA₂) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA₂ is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA₂ and oxLDL in carotid endarterectomy (CEA) tissues and in matched plasmas. In extracts from CEA anatomical segments, the levels of oxLDL were significantly associated with the levels of Lp-PLA₂ protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA₂ mass/activity were most abundant in the carotid bifurcation and internal segments where plaque was most abundant. In extracts from CEA atheroma, the levels of oxLDL and Lp-PLA₂ were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA₂ were negatively correlated (r = – 0.578). The ratio of Lp-PLA₂ to oxLDL was higher in atheromatous tissue (277:1) than in normal tissue (135:1) and plasma (13:1). Immunohistochemical experiments indicated that in plaques, oxLDL and Lp-PLA₂ existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA₂ epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA₂ and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

Supplementary key words carotid endarterectomy • risk factors • atherosclerotic plaque • lysophosphatidylcholine

Abbreviations: apoB-100, apolipoprotein B-100; CEA, carotid endarterectomy; CVD, cardiovascular disease; Lp-PLA₂, lipoprotein-associated phospholipase A₂; oxLDL, oxidized low density lipoprotein; oxPC, oxidized phosphatidylcholine

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