Haematologica 2004;89: supplement no. 8 - Supplements ...

54Oral CommunicationsCO-066NITROPRAVASTATIN (NCX 6550), A NITRIC OXIDE-RELEASINGSTATIN WITH POTENT ANTIPLATELET/ANTITHROMBOTICACTIVITYMomi S, 1 Rossiello MR, 2 Guglielmini G, 1Caracchini R, 1 Monopoli A, 3 Ongini E, 3 Semeraro N, 2Colucci M, 2 Gresele P 11Department of Internal Medicine, Sect. of Internaland Cardiovascular Medicine, University of Perugia,Perugia; 2 Department of Biomedical Sciences, Sect.of General Pathology, University of Bari, Bari; 3 NicOxResearch Institute, Milan, ItalyStatins decrease ischemic cardiovascular eventsboth in hypercholesterolemic and normocholesterolemicsubjects but with a slow onset of action.Recently a new class of drugs combining a statinwith a NO-donating moiety has been described. Aimof our study was to evaluate the in vitro and in vivoeffects of the novel NO-releasing pravastatin (NCX6550) on a number of cellular functions relevant toatherothrombosis. In vitro, NCX6550, but not pravastatin,inhibited dose-dependently: 1) U46619-induced human platelet aggregation in buffer andplasma; 2) collagen-stimulated platelet P-selectinexpression in human whole blood; 3) platelet adhesionto collagen-coated coverslips under high wallshear rate conditions. These effects were associatedwith an enhancement of intraplatelet cGMP andwere abolished by the guanylyl cyclase inhibitor ODQ(10uM). NCX6550 also inhibited dose-dependentlytissue factor (TF) expression in human bloodmononuclear cells exposed to LPS or PMA (85% inhibitionat 50 µM) as assessed by TF antigen and activitydeterminations and by RT-PCR. However, the inhibitionof TF by NCX6550 was not influenced by ODQnor by mevalonolactone (400 uM) or geranyl-geranyl-pyrophosphate(5 uM). Neither pravastatin nora NO-donor (SNP, 10 uM) reduced TF expressionunder our experimental conditions. Treatment withNCX6550 (48 mg/kg i.p.), but not with equimolarpravastatin, significantly reduced mortality (from80% to 37%, p