Indobufen prevents tissue factor expression in human monocytes through a thromboxane-dependent mechanism
Articolo
Data di Pubblicazione:
2006
Citazione:
Indobufen prevents tissue factor expression in human monocytes through a thromboxane-dependent mechanism / S. Eligini, F. Violi, S.S. Barbieri, M. Saliola, M. Brambilla, E. Tremoli, S. Colli. - In: HAEMATOLOGICA. - ISSN 0390-6078. - 91:Suppl. 2(2006 Sep), pp. 86-87. ((Intervento presentato al 19. convegno Congress of the Società Italiana per lo Studio dell’Emostasi e della Trombosi (Siset) tenutosi a Milano nel 2006.
Abstract:
Background. Indobufen is a reversible inhibitor of platelet cyclooxygenase
(Cox) activity, thereby suppressing thromboxane (Tx) synthesis. It
is effective in a broad spectrum of prothrombotic conditions ranging
from graft occlusion after CABG surgery, to restenosis after carotid
endarterectomy, to thromboembolic events in patients with heart disease,
and to intermittent claudication. More recently the ability of indobufen
to suppress the enhanced Tx biosynthesis in a subset of episodes of
platelet activation during the acute phase of unstable angina has been
highlighted. This effect, which is not shared by aspirin, has been attributed
to the inhibition of the inducible Cox isoform (Cox-2), which is
expressed by monocytes in response to a local inflammatory milieu. Aim.
To assess whether indobufen affects tissue factor (TF), the main initiator
of thrombogenesis in vivo, and to investigate the relationship between
Cox-derived products and TF. Methods. Human monocytes were obtained
from peripheral blood of healthy donors. TF was evaluated as procoagulant
activity (PCA) in monocyte lysates. TF protein and mRNA levels
were determined by Western blot and RT-PCR analysis, respectively.
Thromboxane B2 (TxB2) and prostaglandin E2 (PGE2) formation was
measured in monocyte supernatant by immunoenzymatic technique.
Cox-1 and Cox-2 protein level, tyrosine phosphorylation and mitogen
activated protein kinase (MAP-kinase) activation were determined by
Western blot analysis. Results. Indobufen prevents TF expression in
human adherent monocytes exposed to LPS through alteration of
TxB2/PGE2 ratio that occurs through reduction of Tx but not of PGE2 synthesis. Prevention of LPS-induced ERK1/2 phosphorylation is highlighted
as the mechanism responsible for the anti-TF effect of indobufen.
Conclusions: Indobufen down-regulates TF in monocytes. This novel
activity, coupled with the antiplatelet effect, may add benefit for the use
of indobufen in the management of atherothrombosis.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
monocytes ; tissue factor ; thromboxane
Elenco autori:
S. Eligini, F. Violi, S.S. Barbieri, M. Saliola, M. Brambilla, E. Tremoli, S. Colli
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