Department of Anesthesiology and Intensive Care Medicine, Universitätsklinikum Tübingen, Hoppe-Seyler-Straße 3, 72076, Tübingen, Germany.
Institute for Vascular Signalling, Centre for Molecular Medicine, Johann Wolfgang Goethe University, Frankfurt, Germany.
Basic Res Cardiol. 2018 Jan 17;113(2):11. doi: 10.1007/s00395-018-0667-0.
Ischemic preconditioning (IP) is a well-known strategy to protect organs against cell death following ischemia. The previous work has shown that vasodilator-stimulated phosphoprotein (VASP) is involved in cytoskeletal reorganization and that it holds significant importance for the extent of myocardial ischemia reperfusion injury. Yet, the role of VASP during myocardial IP is, to date, not known. We report here that VASP phosphorylation at serine and serine is induced during hypoxia in vitro and during IP in vivo. The preconditioning-induced VASP phosphorylation inactivates the GP IIb/IIIa integrin receptor on platelets, which results in the reduced formation of organ compromising platelet neutrophil complexes. Experiments in chimeric mice confirmed the importance of VASP phosphorylation during myocardial IP. When studying this in VASP animals and in an isolated heart model, we were able to confirm the important role of VASP on myocardial IP. In conclusion, we were able to show that IP-induced VASP phosphorylation in platelets is a protective mechanism against the deleterious effects of ischemia.
缺血预处理（IP）是一种众所周知的策略，可防止器官在缺血后发生细胞死亡。先前的工作表明，血管扩张刺激磷蛋白（VASP）参与细胞骨架重排，对心肌缺血再灌注损伤的程度具有重要意义。然而，迄今为止，VASP 在心肌 IP 中的作用尚不清楚。我们在这里报告，VASP 在体外缺氧和体内 IP 期间的丝氨酸和丝氨酸磷酸化。预处理诱导的 VASP 磷酸化使血小板上的 GP IIb/IIIa 整合素受体失活，导致损害器官的血小板中性粒细胞复合物形成减少。嵌合小鼠实验证实了心肌 IP 过程中 VASP 磷酸化的重要性。在 VASP 动物和离体心脏模型中进行这些研究时，我们能够证实 VASP 在心肌 IP 中的重要作用。总之，我们能够表明，血小板中 IP 诱导的 VASP 磷酸化是一种针对缺血有害影响的保护机制。
