title: Antioxidant and antiplatelet effects of atorvastatin by Nox2 inhibition.
abstract: In recent years, it became evident that reactive oxygen species (ROS) are implicated in the thrombotic process. Statins are lipid-lowering agents able to lower serum cholesterol levels and retard atherosclerotic complications and their clinical sequelae. There is evidence that, among statins, atorvastatin may exert antiplatelet effects by interfering with redox signaling. Recent studies demonstrated that atorvastatin possesses antiplatelet activity via inhibition of platelet formation of NADPH oxidase-derived ROS. This effect results in down-regulation of isoprostanes, which are pro-aggregating molecules, and up-regulation of nitric oxide, which is a platelet inhibitor; such changes occurred immediately after atorvastatin administration and were independent from lipid-lowering property. Experimental and clinical studies documented that statins possess antithrombotic effects, which may account for the reduction of thrombotic-related vascular outcomes. This has been evidenced in different cardiovascular clinical settings such as percutaneous coronary intervention (PCI), myocardial infarction (MI), and venous thrombosis. Future studies should be addressed to analyze if the antiplatelet effect of atorvastatin may preferentially occur at high dosage. Interestingly, the antiplatelet effects of statins could be useful in clinical settings where the clinical efficacy of aspirin and other antiplatelet drugs is still uncertain.
authors.affiliation: I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy. Electronic address: francesco.violi@uniroma1.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.affiliation: I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.affiliation: I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.affiliation: I Clinica Medica, Sapienza University of Rome, Viale del Policlinico 155, Rome 00161, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors* / Q000097:blood; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000097:blood; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000201:enzymology
chemical_list: D000975:Antioxidants; D004791:Enzyme Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008562:Membrane Glycoproteins; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D017382:Reactive Oxygen Species; D000069059:Atorvastatin; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases