Relationship of lipoprotein-associated phospholipase A2 and oxidized low density lipoprotein in carotid atherosclerosis

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

doi:10.1194/jlr.m800342-jlr200

Abstract

Plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Lp-PLA(2) is the sole enzyme responsible for the hydrolysis of oxidized phospholipids on LDL particles in atherosclerotic plaques. We have studied the relationship between Lp-PLA(2) 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-PLA(2) protein (r = 0.497) and activity (r = 0.615). OxLDL and Lp-PLA(2) 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-PLA(2) were significantly correlated (r = 0.634). In matched plasma and atheroma extracts, the levels of Lp-PLA(2) were negatively correlated (r = - 0.578). The ratio of Lp-PLA(2) 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-PLA(2) existed in overlapping but distinctly different distribution. Fluorescence microscopy showed both oxLDL and Lp-PLA(2) epitopes on the same LDL particle in plasma but not in plaque. These results suggest that the relationship between Lp-PLA(2) and oxLDL in the atherosclerotic plaque is different from that in the plasma compartment.

Highlights

Plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and oxidized low density lipoprotein have been identified as risk factors for cardiovascular disease
It was not surprising that Lp-PLA2 enzymatic activity was significantly coupled to oxidized low density lipoprotein (oxLDL) abundance (r = 0.6147, P < 0.0001; Fig. 1F)
The distribution of lipoprotein-associated phospholipase A2 (LpPLA2) and oxLDL was greatest in the bifurcation and internal segments where atherosclerotic lesions were most prevalent

Summary

Introduction

Plasma levels of lipoprotein-associated phospholipase A2 (Lp-PLA2) and oxidized low density lipoprotein (oxLDL) have been identified as risk factors for cardiovascular disease. Immunohistochemical experiments indicated that in plaques, oxLDL and LpPLA2 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. Plasma levels of oxLDL are associated with inflammation and subclinical atherosclerosis development [7] and are correlated with metabolic syndrome risk factors [8]. Lp-PLA2 is a Ca2+-independent serine lipase, known as platelet-activating factor-acetylhydrolase [16] This enzyme has been shown to be a prognostic biomarker for cardiovascular disease (CVD) and coronary heart disease [17,18,19,20].

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