title: Rosuvastatin reduces platelet activation in heart failure: role of NO bioavailability.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medizinische Klinik and Poliklinik I, Universitätsklinikum Würzburg, Bayerische Julius-Maximilians-Universität Würzburg, Germany. a.schaefer@medizin.uni-wuerzburg.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Schäfer
authors.forename: Daniela
authors.initials: D
authors.lastname: Fraccarollo
authors.forename: Martin
authors.initials: M
authors.lastname: Eigenthaler
authors.forename: Piet
authors.initials: P
authors.lastname: Tas
authors.forename: Andreas
authors.initials: A
authors.lastname: Firnschild
authors.forename: Stefan
authors.initials: S
authors.lastname: Frantz
authors.forename: Georg
authors.initials: G
authors.lastname: Ertl
authors.forename: Johann
authors.initials: J
authors.lastname: Bauersachs
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002908:Chronic Disease; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005464:Fluorobenzenes / Q000494:pharmacology*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008840:Microfilament Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015539:Platelet Activation / Q000187:drug effects*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D015815:Cell Adhesion Molecules; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011743:Pyrimidines; D017382:Reactive Oxygen Species; D013449:Sulfonamides; D000098662:Vasodilator-Stimulated Phosphoprotein; D013481:Superoxides; D009569:Nitric Oxide; D000068718:Rosuvastatin Calcium