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. 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.
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 CHFrats and improved by rosuvastatin. In parallel, in vivo VASP phosphorylation reflecting NO bioavailability was significantly attenuated in platelets from CHFrats 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 CHFrats. These mechanisms may contribute to the beneficial effects of statin treatment in CHF.
Authors: Georgios Tsivgoulis; Aristeidis H Katsanos; Vijay K Sharma; Christos Krogias; Robert Mikulik; Konstantinos Vadikolias; Milija Mijajlovic; Apostolos Safouris; Christina Zompola; Simon Faissner; Viktor Weiss; Sotirios Giannopoulos; Spyros Vasdekis; Efstathios Boviatsis; Anne W Alexandrov; Konstantinos Voumvourakis; Andrei V Alexandrov Journal: Neurology Date: 2016-02-24 Impact factor: 9.910
Authors: Pei Yu; Ting Xiong; Christine B Tenedero; Paul Lebeau; Ran Ni; Melissa E MacDonald; Peter L Gross; Richard C Austin; Bernardo L Trigatti Journal: Arterioscler Thromb Vasc Biol Date: 2017-11-21 Impact factor: 8.311
Authors: Travis R Sexton; Eric L Wallace; Tracy E Macaulay; Richard J Charnigo; Virgilio Evangelista; Charles L Campbell; Alison L Bailey; Susan S Smyth Journal: J Thromb Thrombolysis Date: 2015-02 Impact factor: 2.300