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  Maturation of Platelet Function During Murine Fetal Development In Vivo

Margraf, A., Nussbaum, C., Rohwedder, I., Klapproth, S., Kurz, A. R. M., Florian, A., et al. (2017). Maturation of Platelet Function During Murine Fetal Development In Vivo. Arteriosclerosis, Thrombosis, and Vascular Biology: an Official Journal of the American Heart Association, 37(6), 1076-1086. doi:10.1161/ATVBAHA.116.308464.

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 Creators:
Margraf, Andreas1, Author
Nussbaum, Claudia1, Author
Rohwedder, Ina1, Author
Klapproth, Sarah1, Author
Kurz, Angela R. M.1, Author
Florian, Annamaria1, Author
Wiebking, Volker1, Author
Pircher, Joachim1, Author
Pruenster, Monika1, Author
Immler, Roland1, Author
Dietzel, Steffen1, Author
Kremer, Ludmila1, Author
Kiefer, Friedemann1, Author
Moser, Markus2, Author              
Flemmer, Andreas W.1, Author
Quackenbush, Elizabeth1, Author
von Andrian, Ulrich H.1, Author
Sperandio, Markus1, Author
Affiliations:
1external, ou_persistent22              
2Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: PATENT DUCTUS-ARTERIOSUS; NEONATAL PLATELETS; GESTATIONAL-AGE; P-SELECTIN; LEUKOCYTE RECRUITMENT; INTEGRIN ACTIVATION; THROMBUS FORMATION; YOLK-SAC; HEMOSTASIS; MICEHematology; Cardiovascular System & Cardiology; blood platelets; fetal development; hemostasis; intravital microscopy; microcirculation; thrombosis;
 Abstract: Objective-Platelet function has been intensively studied in the adult organism. However, little is known about the function and hemostatic capacity of platelets in the developing fetus as suitable in vivo models are lacking. Approach and Results-To examine fetal platelet function in vivo, we generated a fetal thrombosis model and investigated light/dye-induced thrombus formation by intravital microscopy throughout gestation. We observed that significantly less and unstable thrombi were formed at embryonic day (E) 13.5 compared with E17.5. Flow cytometry revealed significantly lower platelet counts in E13.5 versus E17.5 fetuses versus adult controls. In addition, fetal platelets demonstrated changed activation responses of surface adhesion molecules and reduced P-selectin content and mobilization. Interestingly, we also measured reduced levels of the integrin-activating proteins Kindlin-3, Talin-1, and Rap1 during fetal development. Consistently, fetal platelets demonstrated diminished spreading capacity compared with adults. Transfusion of adult platelets into the fetal circulation led to rapid platelet aggregate formation even in young fetuses. Yet, retrospective data analysis of a neonatal cohort demonstrated no correlation of platelet transfusion with closure of a persistent ductus arteriosus, a process reported to be platelet dependent. Conclusions-Taken together, we demonstrate an ontogenetic regulation of platelet function in vivo with physiologically low platelet numbers and hyporeactivity early during fetal development shedding new light on hemostatic function during fetal life.

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Language(s): eng - English
 Dates: 2017-04-202017
 Publication Status: Published in print
 Pages: 20
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Arteriosclerosis, Thrombosis, and Vascular Biology : an Official Journal of the American Heart Association
  Other : Arterioscleorosis (Dallas)
Source Genre: Journal
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Publ. Info: Philadelphia, PA : Lippincott, Williams & Wilkins
Pages: - Volume / Issue: 37 (6) Sequence Number: - Start / End Page: 1076 - 1086 Identifier: ISSN: 1079-5642
CoNE: https://pure.mpg.de/cone/journals/resource/954927718420