Platelets contribute to postnatal occlusion of the ductus arteriosus
Platelets contribute to postnatal occlusion of the ductus arteriosus
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DOI：
10.1038/nm.2060
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发表时间：
2010-01-01
期刊：
影响因子：
82.9
通讯作者：
Massberg, Steffen
中科院分区：
文献类型：
--
作者：
Echtler, Katrin;Stark, Konstantin;Massberg, Steffen
动脉导管（DA）是肺动脉和主动脉之间的胎儿分流血管，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关闭的事件尚未完全了解。在这里，我们表明，血小板在DA关闭中起着至关重要的作用。使用新生小鼠的活体显微镜，我们观察到，血小板被招募到封闭过程中的DA的管腔方面。血小板粘附或聚集功能障碍或血小板生物合成缺陷的新生儿DA闭合受损。DA闭合缺陷导致左向右分流，肺灌注增加，肺血管重塑和右心室肥大。我们的研究结果表明，血小板是至关重要的DA关闭，促进血栓密封的收缩DA和支持管腔重塑。一项回顾性临床研究显示，血小板减少症是早产人类新生儿DA闭合失败的独立预测因子，表明血小板可能有助于人类DA闭合。
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.