Deutsches Herzzentrum, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany.
Nat Med. 2010 Jan;16(1):75-82. doi: 10.1038/nm.2060. Epub 2009 Dec 6.
The ductus arteriosus (DA) is a fetal shunt vessel between the pulmonary artery and the aorta that closes promptly after birth. Failure of postnatal DA closure is a major cause of morbidity and mortality particularly in preterm neonates. The events leading to DA closure are incompletely understood. Here we show that platelets have an essential role in DA closure. Using intravital microscopy of neonatal mice, we observed that platelets are recruited to the luminal aspect of the DA during closure. DA closure is impaired in neonates with malfunctioning platelet adhesion or aggregation or with defective platelet biogenesis. Defective DA closure resulted in a left-to-right shunt with increased pulmonary perfusion, pulmonary vascular remodeling and right ventricular hypertrophy. Our findings indicate that platelets are crucial for DA closure by promoting thrombotic sealing of the constricted DA and by supporting luminal remodeling. A retrospective clinical study revealed that thrombocytopenia is an independent predictor for failure of DA closure in preterm human newborns, indicating that platelets are likely to contribute to DA closure in humans.
动脉导管（DA）是胎儿肺动脉和主动脉之间的分流血管，出生后迅速关闭。出生后 DA 关闭失败是发病率和死亡率的主要原因，特别是在早产儿中。导致 DA 关闭的事件尚不完全清楚。在这里，我们表明血小板在 DA 关闭中起重要作用。通过对新生小鼠的活体显微镜观察，我们观察到血小板在 DA 闭合过程中募集到管腔的表面。血小板黏附或聚集功能障碍或血小板生成缺陷的新生儿，DA 闭合受损。DA 闭合不良导致左向右分流，肺灌注增加，肺血管重塑和右心室肥厚。我们的研究结果表明，血小板通过促进收缩的 DA 的血栓密封和支持管腔重塑，对于 DA 关闭至关重要。一项回顾性临床研究表明，血小板减少症是早产儿出生后 DA 关闭失败的独立预测因子，这表明血小板可能有助于人类的 DA 关闭。
