Monocyte cyclooxygenase-2 overactivity: a new marker of subclinical atherosclerosis in asymptomatic subjects with cardiovascular risk factors?
OBJECTIVE
Cyclooxygenase-2 (COX-2)-mediated prostaglandin production by activated macrophages is associated with inflammation and atherosclerosis. We investigated the relationship between COX-2-mediated prostaglandin-E2 (PGE2) release, cardiovascular risk factors, and carotid atherosclerosis in apparently healthy subjects.


RESULTS
PGE2 release by lipopolysaccharide-stimulated blood monocytes was measured by ELISA in 291 subjects (76.5% men, mean age 58) who underwent global vascular risk assessment and carotid ultrasonography. COX-2 expression (real-time RT-PCR) was analysed in a subgroup of 100 subjects (76% men, mean age 59). Inducible PGE2 production was associated with smoking and diabetes (P<0.05), but not with arterial hypertension, dyslipidaemia, or obesity. Subjects in the highest tertile of PGE2 (>8.1 ng/mL) had significantly higher mean carotid intima-media thickness (IMT) than those in the lowest tertile (P<0.01). No significant differences among tertiles were observed in the levels of inflammatory markers (C-reactive protein, fibrinogen, and von Willebrand factor). The association between PGE2 and carotid IMT remained statistically significant (P=0.012) after adjustment for a number of cardiovascular and inflammatory risk factors. A correlation between COX-2 expression and PGE2 production was observed (P<0.005).


CONCLUSIONS
COX-2-mediated PGE2 overproduction by stimulated monocytes might provide a new marker of subclinical atherosclerosis in asymptomatic subjects exposed to cardiovascular risk factors.
Beloqui
Oscar
O
Department of Internal Medicine, University Clinic, Clínica Universitaria, Avenida de Pío XII 36, 31008 Pamplona, Spain. obeloqui@unav.ed
Páramo
José A
JA
Orbe
Josune
J
Benito
Alberto
A
Colina
Inmaculada
I
Monasterio
Alberto
A
Díez
Javier
J
D001161:Arteriosclerosis / Q000175:diagnosis*; D015415:Biomarkers / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology; D002340:Carotid Artery Diseases / Q000175:diagnosis*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012307:Risk Factors
D015415:Biomarkers; D008565:Membrane Proteins; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone