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NCX4016 (NO-aspirin) inhibits thromboxane biosynthesis and tissue factor expressionand activity in human monocytes.

Pietro Minuz, Maurizio Degan, Stefania Gaino, Alessandra Meneguzzi, Valeria Zuliani, Clara Lechi Santonastaso, Piero Del Soldato, Alessandro Lechi

Med Sci Monit 2001; 7(4): BR573-577

ID: 421101

BACKGROUND: NCX4016 (2 acetoxy-benzoate 2-(2-nitroxymethyl)-phenyl ester,NicOx S.A., France) is an antithrombotic agent chemically related to acetylsalicylic acid (ASA). We hypothesisedthat NCX4016, being able to release nitric oxide (NO) and to inhibit cyclo-oxygenase, might inhibit theprothrombotic function in human monocytes.MATERIAL AND METHODS: The effects of NCX4016 and ASA on therelease of thromboxane (TX) B2 and tissue factor expression and activity were compared using adherenthuman monocytes. The tested drugs were added before stimulation with 10 Kg/ml LPS and incubation lasted6 hours. TXB2 concentration was measured by RIA in the supernatant of cultured cells. Immunoreactivetissue factor (TF) concentration was determined by enzyme-linked immunoassay and TF activity was assayedby measuring the peptidyl activity of the tissue factor/ factor VII complex.RESULTS: Both ASA and NCX401610-300 Kmol/L dose-dependently reduced TXB2 release. NCX4016 activity was comparable to that of equimolarASA. Part of the activity of NCX4016 up to 100 Kmol/L was prevented by 10 Kml/L ODQ, inhibitor of cGMPgeneration. Immunoreactive TF was dose-dependently inhibited by 300 Kmol/L NCX4016, but not by ASA. Alsotissue TF activity was reduced by 300 Kmol/L NCX4016, but not by ASA.CONCLUSIONS: The present resultsindicate that NCX4016 not only has anti-platelet effects but also inhibits prothrombotic activities inhuman monocytes, partly via NO-dependent mechanisms. NCX4016 may prove effective in the clinical settingof athero-thrombosis.

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