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

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

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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-PLA 2 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-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.

Original languageEnglish (US)
Pages (from-to)1735-1743
Number of pages9
JournalJournal of lipid research
Volume50
Issue number9
DOIs
StatePublished - 2009

Keywords

  • Atherosclerotic plaque
  • Carotid endarterectomy
  • Lysophosphatidylcholine
  • Risk factors

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

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