Published online before print March 10, 2005, doi: 10.1161/01.ATV.0000161926.43967.df
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© 2005 American Heart Association, Inc.
Thrombosis |
Rosuvastatin Reduces Platelet Activation in Heart Failure
Role of NO Bioavailability
From the Medizinische Klinik und Poliklinik I (A.S., D.F., A.F., S.F., G.E., J.B.), Universitätsklinikum Würzburg, Bayerische Julius-Maximilians-Universität Würzburg, Germany; Institut für Klinische Biochemie und Pathobiochemie (M.E.), Bayerische Julius-Maximilians-Universität Würzburg, Germany; and Klinik für Anästhesiologie (P.T.), Universitätsklinikum Würzburg, Bayerische Julius-Maximilians-Universität Würzburg, Germany
Correspondence to Andreas Schäfer, MD, Medizinische Klinik and Poliklinik 1, Universitätsklinik Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. E-mail a.schaefer{at}medizin.uni-wuerzburg.de
Objectives— Endothelial dysfunction and platelet activation are part of the cardiovascular phenotype in congestive heart failure (CHF). We investigated whether 3-hydroxy-3-methylglutaryl–coenzyme A (HMG-CoA) reductase inhibition would beneficially modulate vascular NO bioavailability and platelet activation in experimental CHF.
Methods and Results— Chronic myocardial infarction was induced by coronary ligation in male Wistar rats. Animals were either treated with placebo or the HMG-CoA reductase inhibitor rosuvastatin. After 10 weeks, hemodynamic assessment was performed and endothelial function was determined in organ bath studies. NO bioavailability was assessed by in vivo platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation. Markers of platelet degranulation (surface expression of P-selectin and glycoprotein 53) were determined as well as the amount of circulating platelet–leukocyte aggregates. Endothelium-dependent, acetylcholine-induced vasorelaxation was significantly impaired in aortic rings from CHF rats and improved by rosuvastatin. In parallel, in vivo VASP phosphorylation reflecting NO bioavailability was significantly attenuated in platelets from CHF rats and normalized by rosuvastatin. Platelet activation, which was increased in CHF, was reduced by treatment with rosuvastatin.
Conclusion— HMG-CoA reductase inhibition improved endothelial function, increased systemic NO bioavailability and inhibited exaggerated platelet activation in CHF rats. These mechanisms may contribute to the beneficial effects of statin treatment in CHF.
Congestive heart failure is associated with progressive vascular endothelial dysfunction, reduced systemic NO bioavailability, and platelet activation in vivo. Chronic treatment with the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor rosuvastatin in rats with heart failure after myocardial infarction improved NO bioavailability and reduced platelet activation.
Key Words: endothelial dysfunction • nitric oxide • platelet activation • CHF • HMG-CoA reductase inhibition
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