Statins as regulators of redox signaling in platelets

Reactive oxidant species (ROS) are highly reactive molecules produced by several cell lines including platelets and serve as second messenger for intracellular signaling. In recent years it became evident that ROS are also implicated in the thrombotic process. Statins are lipid lowering molecules which reduce serum cholesterol and retard atherosclerotic complication and its clinical sequelae. However there is evidence that statins may exert an antiplatelet effects by interfering with redox signaling.

Experimental and clinical studies provided evidence that intra-platelet ROS formation is implicated in the process of thrombosis, as impaired ROS neutralization is associated with serious thrombotic complication and eventually death. Recent studies demonstrated that statins possess antiplatelet activity via inhibition of platelet NADPH oxidase-derived ROS formation. 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 statin's administration and were independent from lipid lowering property.

Experimental and clinical studies documented that statins possess an antithrombotic effects which may account for thrombotic-related vascular outcomes. This has been evidenced in clinical settings such as percutaneous coronary intervention, myocardial infarction and venous thrombosis. It is still unclear, however, if the statin's antithrombotic effect is dose-related.

Future studies should be addressed to analyze if the antiplatelet effect of statins may preferentially occur at high dosage of statins. Furthermore, the antiplatelet effects of statins could turn useful in clinical settings where the clinical efficacy of aspirin and other antiplatelet drugs are still uncertain.