Neopterin induces pro-atherothrombotic phenotype in human coronary endothelial cells.
BACKGROUND
Inflammation plays a pivotal role in atherothrombosis. Recent data indicate that serum levels of neopterin, a marker of inflammation and immune modulator secreted by monocytes/macrophages, are elevated in patients with acute coronary syndromes and seem to be a prognostic marker for major cardiovascular events. The aim of the present study was to determine whether neopterin might affect the thrombotic and atherosclerotic characteristics of human coronary artery endothelial cells (HCAECs).


RESULTS
In HCAECs, neopterin induced TF-mRNA transcription as demonstrated by real time polymerase chain reaction and expression of functionally active tissue factor (TF) as demonstrated by procoagulant activity assay, and of cellular adhesion molecules (CAMs) as demonstrated by FACS analysis, in a dose-dependent fashion. These neopterin effects were prevented by lovastatin, a HMG-CoA reductase inhibitor. Neopterin-induced TF and CAMs expression was mediated by oxygen free radicals through the activation of the transcription factor, nuclear factor-kappa B (NF-kappaB), as demonstrated by electrophoretic mobility shift assay and by suppression of CAMs and TF expression by superoxide dismutase and by NF-kappaB inhibitor, pyrrolidine-dithio-carbamate ammonium.


CONCLUSIONS
These data indicate that neopterin exerts direct effects on HCAECs by promoting CAMs and TF expression and support the hypothesis that neopterin, besides representing a marker of inflammation, might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation.
Cirillo
P
P
Division of Cardiology, University of Naples 'Federico II', Naples, Italy. pcirillo@unina.it
Pacileo
M
M
DE Rosa
S
S
Calabrò
P
P
Gargiulo
A
A
Angri
V
V
Granato-Corigliano
F
F
Fiorentino
I
I
Prevete
N
N
DE Palma
R
R
Mauro
C
C
Leonardi
A
A
Chiariello
M
M
D002448:Cell Adhesion; D003331:Coronary Vessels / Q000166:cytology / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000473:pathology*; D006801:Humans; D007249:Inflammation; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019798:Neopterin / Q000494:pharmacology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013927:Thrombosis / Q000473:pathology*; D014158:Transcription, Genetic
D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D019798:Neopterin