I Clinica Medica, Sapienza University , Roma, Italy .
Antioxid Redox Signal. 2014 Mar 10;20(8):1300-12. doi: 10.1089/ars.2013.5527. Epub 2013 Oct 4.
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.
活性氧（ROS）是几种细胞系（包括血小板）产生的高反应性分子，作为细胞内信号转导的第二信使。近年来，ROS 也被认为与血栓形成过程有关。他汀类药物是降低血脂的分子，可以降低血清胆固醇并延缓动脉粥样硬化并发症及其临床后果。然而，有证据表明他汀类药物可能通过干扰氧化还原信号而发挥抗血小板作用。
实验和临床研究提供的证据表明，血小板内 ROS 的形成与血栓形成过程有关，因为 ROS 中和作用受损与严重的血栓并发症并最终导致死亡有关。最近的研究表明，他汀类药物通过抑制血小板 NADPH 氧化酶衍生的 ROS 形成具有抗血小板活性。这种作用导致具有促聚集作用的物质异前列烷的下调和血小板抑制剂一氧化氮的上调；这种变化在他汀类药物给药后立即发生，并且独立于降脂作用。
实验和临床研究证明他汀类药物具有抗血栓作用，这可能与血栓相关的血管结果有关。这在经皮冠状动脉介入治疗、心肌梗死和静脉血栓形成等临床环境中得到了证实。然而，他汀类药物的抗血栓作用是否与剂量有关尚不清楚。
未来的研究应该分析他汀类药物的抗血小板作用是否可能优先发生在高剂量的他汀类药物。此外，他汀类药物的抗血小板作用可能在阿司匹林和其他抗血小板药物的临床疗效仍不确定的临床环境中变得有用。
