A previous study has shown that simvastatin reduces in vivo clotting activation and monocyte tissue factor (TF) expression. This effect, however, was only in part attributable to the reduction of serum cholesterol, suggesting that more than one mechanism may be involved. Furthermore, it was not investigated if the inhibition of clotting activation was dependent upon the reduced expression of monocyte TF. In order to assess if simvastatin directly affects clotting activation, we developed an in vitro method in which clotting system is activated by monocytes stimulated with LPS. Monocytes were prepared from blood taken from healthy volunteers or patients with hypercholesterolemia and incubated with heparinized plasma plus either simvastatin (0.01-10 mu M) or medium as control. Samples were then stimulated with LPS (4 mu g/ml) and after 6 h the rate of thrombin generation, assessed by prothrombin fragment (F) 1 + 2, was measured. In separate experiments, we measured the expression of TF by monocytes which were incubated with simvastatin and then stimulated with LPS. The study showed that compared to control, LPS-stimulated monocytes induced abundant formation of F1 + 2, which was inhibited by simvastatin in a dose-dependent manner. Simvastatin also inhibited dose dependently the monocyte expression of TF. This study suggests that simvastatin inhibits the rate of thrombin generation by directly interfering with the monocyte expression of TF. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Inhibition of tissue-factor-mediated thrombin generation by simvastatin / Ferro, Domenico; Basili, Stefania; Alessandri, Cesare; Doloretta, Cara; Violi, Francesco. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - STAMPA. - 149:1(2000), pp. 111-116. [10.1016/s0021-9150(99)00291-9]

Inhibition of tissue-factor-mediated thrombin generation by simvastatin

FERRO, Domenico;BASILI, Stefania;ALESSANDRI, Cesare;VIOLI, Francesco
2000

Abstract

A previous study has shown that simvastatin reduces in vivo clotting activation and monocyte tissue factor (TF) expression. This effect, however, was only in part attributable to the reduction of serum cholesterol, suggesting that more than one mechanism may be involved. Furthermore, it was not investigated if the inhibition of clotting activation was dependent upon the reduced expression of monocyte TF. In order to assess if simvastatin directly affects clotting activation, we developed an in vitro method in which clotting system is activated by monocytes stimulated with LPS. Monocytes were prepared from blood taken from healthy volunteers or patients with hypercholesterolemia and incubated with heparinized plasma plus either simvastatin (0.01-10 mu M) or medium as control. Samples were then stimulated with LPS (4 mu g/ml) and after 6 h the rate of thrombin generation, assessed by prothrombin fragment (F) 1 + 2, was measured. In separate experiments, we measured the expression of TF by monocytes which were incubated with simvastatin and then stimulated with LPS. The study showed that compared to control, LPS-stimulated monocytes induced abundant formation of F1 + 2, which was inhibited by simvastatin in a dose-dependent manner. Simvastatin also inhibited dose dependently the monocyte expression of TF. This study suggests that simvastatin inhibits the rate of thrombin generation by directly interfering with the monocyte expression of TF. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.
2000
monocyte tissue factor expression; prothrombin fragment f1 + 2; prothrombin fragment f1+2; simvastatin
01 Pubblicazione su rivista::01a Articolo in rivista
Inhibition of tissue-factor-mediated thrombin generation by simvastatin / Ferro, Domenico; Basili, Stefania; Alessandri, Cesare; Doloretta, Cara; Violi, Francesco. - In: ATHEROSCLEROSIS. - ISSN 0021-9150. - STAMPA. - 149:1(2000), pp. 111-116. [10.1016/s0021-9150(99)00291-9]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/252025
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