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Rosuvastatin reduces platelet recruitment by inhibiting NADPH oxidase activation.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2012 Dec 15; Vol. 84 (12), pp. 1635-42. Date of Electronic Publication: 2012 Sep 26. - Publication Year :
- 2012
-
Abstract
- Rosuvastatin increased vascular endothelial NO and attenuated platelet activation after ischemia-reperfusion in mice; nevertheless, the influence of rosuvastatin on the activation of human platelets and the underlying mechanism has never been investigated. In an in vitro study platelets from 8 healthy donors were incubated with scalar concentrations of rosuvastatin (1-10 μM) before activation. Platelet recruitment (PR), that mimics the propagation of platelet aggregation and is dependent upon isoprostane formation, was investigated. PR was inhibited by rosuvastatin in concentration-dependent manner concomitantly with down-regulation of platelet release of the pro-thrombotic molecule CD40L. This effect was associated with lower production of platelet reactive oxygen species (ROS), isoprostane and activation of the glycoprotein IIb/IIIa and was counteracted by exogenous addition of isoprostanes. Conversely, rosuvastatin concentration-dependently increased platelet NO. Platelet isoprostane formation mainly depends from NADPH oxidase. Rosuvastatin concentration-dependently inhibited platelet sNOX2-dp release, a specific marker of NADPH oxidase activation, PKC phosphorylation and p47(phox) translocation from cytosol to membranes. In an ex vivo study 10 hypercolesterolemic patients were randomly allocated to diet or rosuvastatin (20 mg). We observed that as early as 2h after rosuvastatin PR, platelet isoprostanes formation, platelet CD40L and sNOX2-dp decreased while platelet NO increased; no changes were detected in diet-assigned patients. This study shows that in vitro rosuvastatin impairs platelet activation via inhibition of NOX2-derived oxidative stress. This effect, which is associated ex vivo with acute inhibition of platelet activation, suggests that rosuvastatin behaves as an antiplatelet drug.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Blood Platelets enzymology
Blood Platelets metabolism
Dose-Response Relationship, Drug
Female
Flow Cytometry
Humans
In Vitro Techniques
Male
Middle Aged
Nitric Oxide biosynthesis
Reactive Oxygen Species metabolism
Rosuvastatin Calcium
Blood Platelets drug effects
Enzyme Activation drug effects
Fluorobenzenes pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
NADPH Oxidases metabolism
Pyrimidines pharmacology
Sulfonamides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 84
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 23022230
- Full Text :
- https://doi.org/10.1016/j.bcp.2012.09.011