Abstract：
Myocardial cell death is the hallmark of myocardial infarction. In the process of myocardial injury, platelets contribute to the pathogenesis by triggering intense inflammatory responses. Yet, it is still unclear if platelets regulate cardiomyocyte death directly, thereby exacerbating myocardial injury in myocardial infarction.
We describe a mechanism underlying the correlative association between platelets accumulation and myocardial cell death by using myocardial infarction mouse model and patient specimens.
Myocardial infarction induces platelets internalization, resulting in the release of miR-223-3p, a platelet-enriched miRNA. By targeting the ACSL3, miR-223-3p delivered by internalized platelets cause the reduction of stearic acid-phosphatidylcholine in cardiomyocytes. The presence of stearic acid-phosphatidylcholine protects cardiomyocytes against ferroptosis.
Our work reveals a novel mechanism of platelet-mediated myocardial injury, highlighting antiplatelet therapies could potentially represent a multimechanism treatment of myocardial infarction, and implying ferroptosis being considered as novel target for therapeutics.
We describe a mechanism underlying the correlative association between platelets accumulation and myocardial cell death by using myocardial infarction mouse model and patient specimens.
Myocardial infarction induces platelets internalization, resulting in the release of miR-223-3p, a platelet-enriched miRNA. By targeting the ACSL3, miR-223-3p delivered by internalized platelets cause the reduction of stearic acid-phosphatidylcholine in cardiomyocytes. The presence of stearic acid-phosphatidylcholine protects cardiomyocytes against ferroptosis.
Our work reveals a novel mechanism of platelet-mediated myocardial injury, highlighting antiplatelet therapies could potentially represent a multimechanism treatment of myocardial infarction, and implying ferroptosis being considered as novel target for therapeutics.
摘要：
背景：心肌细胞死亡是心肌梗死的标志。在心肌损伤的过程中,血小板通过引发强烈的炎症反应参与发病机制。然而，目前尚不清楚血小板是否直接调节心肌细胞死亡，从而加重心肌梗死的心肌损伤。
方法：我们通过使用心肌梗死小鼠模型和患者标本描述了血小板积累与心肌细胞死亡之间相关关联的潜在机制。
结果：心肌梗死诱导血小板内化，导致miR-223-3p的释放，富含血小板的miRNA。通过靶向ACSL3,由内在化血小板递送的miR-223-3p引起心肌细胞中硬脂酸-磷脂酰胆碱的减少。硬脂酸-磷脂酰胆碱的存在保护心肌细胞免于铁凋亡。
结论：我们的工作揭示了血小板介导的心肌损伤的新机制，强调抗血小板治疗可能代表心肌梗死的多机制治疗，并暗示铁性凋亡被认为是治疗的新靶标。
方法：我们通过使用心肌梗死小鼠模型和患者标本描述了血小板积累与心肌细胞死亡之间相关关联的潜在机制。
结果：心肌梗死诱导血小板内化，导致miR-223-3p的释放，富含血小板的miRNA。通过靶向ACSL3,由内在化血小板递送的miR-223-3p引起心肌细胞中硬脂酸-磷脂酰胆碱的减少。硬脂酸-磷脂酰胆碱的存在保护心肌细胞免于铁凋亡。
结论：我们的工作揭示了血小板介导的心肌损伤的新机制，强调抗血小板治疗可能代表心肌梗死的多机制治疗，并暗示铁性凋亡被认为是治疗的新靶标。
