Expression of lipoprotein-associated phospholipase A(2) in carotid artery plaques predicts long-term cardiac outcome.
OBJECTIVE
The aim was to test the hypothesis that carotid artery plaque expression of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) predicts cardiac events.


RESULTS
Prospective cohort study of 162 consecutive patients undergoing elective carotid endarterectomy. Lipoprotein-associated phospholipase A(2) content was quantified by immunoblotting and lysophosphatidylcholine (lysoPC) by liquid chromatography tandem mass spectrometry. Additional biomolecular profiling by immunoblotting included C-reactive protein, p67phox, and matrix metalloproteinase-2 and -9. Macrophage plaque content was determined by quantitative immunostaining, plaque collagen content by quantitative Sirius red staining. Follow-up for cardiac death and non-fatal acute myocardial infarction was accomplished over a period of 48 +/- 14 months. Expression of Lp-PLA(2) and lysoPC was higher in carotid plaques of patients with than without cardiac events [median 1.6 (25th, 75th percentile 0.9, 2.5) vs. 0.8 (0.5, 2.0), P = 0.01 and 413 (281, 443) vs. 226 (96, 351) mmol/L, P = 0.03]. Smoking and point increase in carotid Lp-PLA(2) expression but no other traditional cardiovascular risk factor, histological or molecular marker remained predictive of cardiac events in the multivariate Cox proportional hazard analyses [HR 3.65 (1.36-9.83), P = 0.01 and HR 1.34 (1.01-1.77), P = 0.039]. Carotid plaque Lp-PLA(2) expression above the median constituted a more than three times higher risk for cardiac events [HR 3.39 (1.13-10.17), P = 0.03].


CONCLUSIONS
Lipoprotein-associated phospholipase A(2) expression in carotid artery plaques is a predictor of long-term cardiac outcome. The current study supports the concept of atherosclerosis as a systemic disease with multi-focal complications and personalized medicine.
Herrmann
Joerg
J
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Mannheim
Dallit
D
Wohlert
Christine
C
Versari
Daniele
D
Meyer
Fredric B
FB
McConnell
Joseph P
JP
Gössl
Mario
M
Lerman
Lilach O
LO
Lerman
Amir
A
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000378:metabolism*; D000368:Aged; D050197:Atherosclerosis / Q000201:enzymology; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000201:enzymology* / Q000473:pathology; D016893:Carotid Stenosis / Q000201:enzymology* / Q000473:pathology; D016894:Endarterectomy, Carotid; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism
D015415:Biomarkers; D008244:Lysophosphatidylcholines; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D002097:C-Reactive Protein; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
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