揭示血小板 Mfsd2b 释放的 S1P 在人类和鼠心肌梗死中的隐匿性心脏保护作用。
Revealing concealed cardioprotection by platelet Mfsd2b-released S1P in human and murine myocardial infarction.
机构信息
Department of Cardiology, Pulmonology, and Vascular Medicine, University Hospital Düsseldorf, Medical Faculty of the Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
CARID, Cardiovascular Research Institute Düsseldorf, Medical Faculty and University Hospital, Düsseldorf, Germany.
出版信息
Nat Commun. 2023 Apr 26;14(1):2404. doi: 10.1038/s41467-023-38069-5.
Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate with cardiovascular mortality and infarct size in STEMI patients over 12 months. Experimentally, administration of supernatant from activated platelets reduces infarct size in murine AMI, which is blunted in platelets deficient for S1P export (Mfsd2b) or production (Sphk1) and in mice deficient for cardiomyocyte S1P receptor 1 (S1P). Our study reveals an exploitable therapeutic window in antiplatelet therapy in AMI as the GPIIb/IIIa antagonist tirofiban preserves S1P release and cardioprotection, whereas the P2Y12 antagonist cangrelor does not. Here, we report that platelet-mediated intrinsic cardioprotection is an exciting therapeutic paradigm reaching beyond AMI, the benefits of which may need to be considered in all antiplatelet therapies.
抗血小板药物是急性心肌梗死（AMI）的标准治疗方法。然而，它可能掩盖了激活血小板分泌组的有益特性。我们发现血小板是 AMI 期间溶血磷脂酸（S1P）爆发的主要来源，并且发现其幅度与 STEMI 患者 12 个月内的心血管死亡率和梗死面积呈正相关。在实验中，给予激活血小板的上清液可减少小鼠 AMI 的梗死面积，而 S1P 外排（Mfsd2b）或产生（Sphk1）缺陷的血小板或心肌细胞 S1P 受体 1（S1P）缺陷的小鼠则会减弱该作用。我们的研究揭示了 AMI 中抗血小板治疗的一个可利用的治疗窗口，因为 GPIIb/IIIa 拮抗剂替罗非班可保留 S1P 释放和心脏保护作用，而 P2Y12 拮抗剂坎格雷洛则没有。在这里，我们报告说，血小板介导的内在心脏保护是一种令人兴奋的治疗范例，超越了 AMI，所有抗血小板治疗都需要考虑其益处。
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