title: Platelets contribute to postnatal occlusion of the ductus arteriosus.
abstract: 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.
authors: Deutsches Herzzentrum, Klinik für Herz- und Kreislauferkrankungen, Technische Universität, Munich, Germany.
authors: Katrin
authors: K
authors: Echtler
authors: Konstantin
authors: K
authors: Stark
authors: Michael
authors: M
authors: Lorenz
authors: Sandra
authors: S
authors: Kerstan
authors: Axel
authors: A
authors: Walch
authors: Luise
authors: L
authors: Jennen
authors: Martina
authors: M
authors: Rudelius
authors: Stefan
authors: S
authors: Seidl
authors: Elisabeth
authors: E
authors: Kremmer
authors: Nikla R
authors: NR
authors: Emambokus
authors: Marie-Luise
authors: ML
authors: von Bruehl
authors: Jon
authors: J
authors: Frampton
authors: Berend
authors: B
authors: Isermann
authors: Orsolya
authors: O
authors: Genzel-Boroviczény
authors: Christian
authors: C
authors: Schreiber
authors: Julinda
authors: J
authors: Mehilli
authors: Adnan
authors: A
authors: Kastrati
authors: Markus
authors: M
authors: Schwaiger
authors: Ramesh A
authors: RA
authors: Shivdasani
authors: Steffen
authors: S
authors: Massberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D004373:Ductus Arteriosus / Q000187:drug effects / Q000196:embryology*; D004374:Ductus Arteriosus, Patent / Q000209:etiology; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007231:Infant, Newborn / Q000254:growth & development; D051379:Mice; D010973:Platelet Adhesiveness / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D010976:Platelet Count; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin