NCX4016 (NO-aspirin) inhibits thromboxane biosynthesis and tissue factor expression and activity in human monocytes.
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 hypothesised that NCX4016, being able to release nitric oxide (NO) and to inhibit cyclo-oxygenase, might inhibit the prothrombotic function in human monocytes.


METHODS
The effects of NCX4016 and ASA on the release of thromboxane (TX) B2 and tissue factor expression and activity were compared using adherent human monocytes. The tested drugs were added before stimulation with 10 Kg/ml LPS and incubation lasted 6 hours. TXB2 concentration was measured by RIA in the supernatant of cultured cells. Immunoreactive tissue factor (TF) concentration was determined by enzyme-linked immunoassay and TF activity was assayed by measuring the peptidyl activity of the tissue factor/ factor VII complex.


RESULTS
Both ASA and NCX4016 10-300 Kmol/L dose-dependently reduced TXB2 release. NCX4016 activity was comparable to that of equimolar ASA. Part of the activity of NCX4016 up to 100 Kmol/L was prevented by 10 Kml/L ODQ, inhibitor of cGMP generation. Immunoreactive TF was dose-dependently inhibited by 300 Kmol/L NCX4016, but not by ASA. Also tissue TF activity was reduced by 300 Kmol/L NCX4016, but not by ASA.


CONCLUSIONS
The present results indicate that NCX4016 not only has anti-platelet effects but also inhibits prothrombotic activities in human monocytes, partly via NO-dependent mechanisms. NCX4016 may prove effective in the clinical setting of athero-thrombosis.
Minuz
P
P
Department of Biomedical and Surgical Sciences, University of Verona, Italy. minuz@borgoroma.univr.it
Degan
M
M
Gaino
S
S
Meneguzzi
A
A
Zuliani
V
V
Lechi Santonastaso
C
C
Del Soldato
P
P
Lechi
A
A
D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013925:Thromboplastin / Q000378:metabolism*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
C093285:NOC 18; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D013925:Thromboplastin; C102148:nitroaspirin; D001241:Aspirin