Relationship of lipoprotein-associated phospholipase A2 and oxidized low density lipoprotein in carotid atherosclerosis.
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.
Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
Kasey C
KC
Vickers
Colin T
CT
Maguire
Robert
R
Wolfert
Alan R
AR
Burns
Michael
M
Reardon
Richard
R
Geis
Paul
P
Holvoet
Joel D
JD
Morrisett
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood / Q000378:metabolism*; D000368:Aged; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D001692:Biological Transport; D002339:Carotid Arteries / Q000166:cytology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D002340:Carotid Artery Diseases / Q000097:blood / Q000378:metabolism* / Q000473:pathology; D016894:Endarterectomy, Carotid; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase