Centro Cardiologico Monzino, IRCCS, Milan, Italy.
Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy.
Oxid Med Cell Longev. 2017;2017:9258937. doi: 10.1155/2017/9258937. Epub 2017 Nov 28.
Environmental chronic stress (ECS) has been identified as a trigger of acute coronary syndromes (ACS). Changes in redox balance, enhanced reactive oxygen species (ROS) production, and platelet hyperreactivity were detected in both ECS and ACS. However, the mechanisms by which ECS predisposes to thrombosis are not fully understood. Here, we investigated the impact of ECS on platelet activation and megakaryopoiesis in mice and the effect of Apocynin in this experimental setting. ECS induced by 4 days of forced swimming stress (FSS) treatment predisposed to arterial thrombosis and increased oxidative stress (e.g., plasma malondialdehyde levels). Interestingly, Apocynin treatment prevented these alterations. In addition, FSS induced abnormal megakaryopoiesis increasing the number and the maturation state of bone marrow megakaryocytes (MKs) and affecting circulating platelets. In particular, a higher number of large and reticulated platelets with marked functional activation were detected after FSS. Apocynin decreased the total MK number and prevented their ability to generate ROS without affecting the percentage of CD42d cells, and it reduced the platelet hyperactivation in stressed mice. In conclusion, Apocynin restores the physiological megakaryopoiesis and platelet behavior, preventing the detrimental effect of chronic stress on thrombosis, suggesting its potential use in the occurrence of thrombosis associated with ECS.
环境慢性应激（ECS）已被确定为急性冠状动脉综合征（ACS）的触发因素。在 ECS 和 ACS 中都检测到氧化还原平衡的变化、活性氧（ROS）产生增加和血小板高反应性。然而，ECS 导致血栓形成的机制尚未完全阐明。在这里，我们研究了 ECS 对小鼠血小板活化和巨核细胞生成的影响以及 Apocynin 在这种实验环境中的作用。通过 4 天的强迫游泳应激（FSS）处理诱导的 ECS 易患动脉血栓形成并增加氧化应激（例如，血浆丙二醛水平）。有趣的是，Apocynin 治疗可预防这些改变。此外，FSS 诱导异常的巨核细胞生成，增加骨髓巨核细胞（MK）的数量和成熟状态，并影响循环血小板。特别是，在 FSS 后检测到大量具有明显功能激活的大而网织状血小板。Apocynin 降低了总 MK 数量，并阻止了它们产生 ROS 的能力，而不影响 CD42d 细胞的百分比，并且减少了应激小鼠的血小板过度激活。总之，Apocynin 恢复了生理巨核细胞生成和血小板行为，防止慢性应激对血栓形成的不利影响，表明其在与 ECS 相关的血栓形成中的潜在用途。
