摘要
Aims: 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. Methods and 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.
Aims: 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. Methods and 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.
