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Atorvastatin delays murine platelet activation in vivo even in the absence of endothelial NO synthase.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2012 Nov; Vol. 32 (11), pp. 2609-15. Date of Electronic Publication: 2012 Sep 20. - Publication Year :
- 2012
-
Abstract
- Objective: Statins decrease mortality in patients with vascular disorders, and evidence for the pleiotropic effects of statins is accumulating. Statins enhance endothelial NO synthase (eNOS) expression, thereby attenuating platelet activation and thrombus formation. Our goal was to determine whether statins have eNOS-independent effects on platelet activation.<br />Methods and Results: Wild-type and eNOS-deficient mice were given a 14-day course of oral atorvastatin, and platelet activation was evaluated in vitro and in vivo. Whereas in wild-type mice atorvastatin inhibited platelet activation in vitro in response to numerous agonists, in eNOS-deficient mice, atorvastatin inhibited only thrombin-induced and protease-activated receptor 4 agonist peptide-induced platelet activation. Consistent with an eNOS-independent effect, atorvastatin inhibited platelet activation in vivo in both wild-type and eNOS-deficient mice.<br />Conclusions: Atorvastatin inhibits platelet activation via eNOS-dependent and eNOS-independent mechanisms with the latter restricted to protease-activated receptor 4-induced activation downstream to the receptor.
- Subjects :
- Administration, Oral
Animals
Atorvastatin
Blood Platelets metabolism
Cyclic GMP metabolism
Heptanoic Acids administration & dosage
Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage
Mice
Mice, Inbred C57BL
Mice, Knockout
Nitric Oxide Synthase Type III genetics
P-Selectin metabolism
Platelet Aggregation drug effects
Platelet Aggregation Inhibitors administration & dosage
Platelet Function Tests
Platelet Membrane Glycoprotein IIb metabolism
Pyrroles administration & dosage
Receptors, Thrombin drug effects
Receptors, Thrombin metabolism
Signal Transduction drug effects
Thrombin metabolism
Time Factors
Blood Platelets drug effects
Heptanoic Acids pharmacology
Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology
Nitric Oxide Synthase Type III deficiency
Platelet Activation drug effects
Platelet Aggregation Inhibitors pharmacology
Pyrroles pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4636
- Volume :
- 32
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 22995523
- Full Text :
- https://doi.org/10.1161/ATVBAHA.112.300090