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Ibuprofen and indomethacin differentially regulate vascular endothelial growth factor and its receptors in ductus arteriosus endothelial cells

Published online by Cambridge University Press:  04 December 2017

Hannes Sallmon ,
Sandra Akanbi ,
Sven C. Weber ,
Alexander Gratopp ,
Cornelia Rheinländer  and
Petra Koehne
Hannes Sallmon*
Affiliation:
Department of Neonatology, Charité University Medical Center, Berlin, Germany
Sandra Akanbi
Affiliation:
Department of Neonatology, Charité University Medical Center, Berlin, Germany
Sven C. Weber
Affiliation:
Department of Pediatrics/Neonatology and Pediatric Intensive Care Medicine, University of Greifswald, Greifswald, Germany
Alexander Gratopp
Affiliation:
Division of Pediatric Emergency and Intensive Care Medicine, Charité University Medical Center, Berlin, Germany
Cornelia Rheinländer
Affiliation:
Department of Neonatology, Charité University Medical Center, Berlin, Germany
Petra Koehne
Affiliation:
Department of Neonatology, Charité University Medical Center, Berlin, Germany
*
Correspondence to: H. Sallmon, MD, Department of Neonatology, Charité – Universitätsmedizin Berlin, Augustenburger Platz 1, 13353 Berlin, Germany. Tel: +49 450 566 122; Fax: +49 450 566 922; E-mail: hannes.sallmon@charite.de
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Abstract

Background

Cyclooxygenase inhibitors are widely applied to facilitate ductal closure in preterm infants. The mechanisms that lead to patent ductus arteriosus closure are incompletely understood. Vascular endothelial growth factor plays pivotal roles during ductal closure and remodelling.

Aim

The aim of this study was to investigate the effects of ibuprofen and indomethacin on the expression of vascular endothelial growth factor and its receptors in a primary rat ductus arteriosus endothelial cell culture.

Methods

Protein expression of vascular endothelial growth factor and vascular endothelial growth factor receptor 1 and 2 was confirmed in rat ductus arteriosus and aorta by immunofluorescence staining. Fetal rat endothelial cells were isolated from ductus arteriosus and aorta using immunomagnetic cell sorting and treated with ibuprofen or indomethacin. mRNA expression levels were assessed by quantitative polymerase chain reaction analysis.

Results

In ductal endothelial cells, ibuprofen significantly induced vascular endothelial growth factor and its receptor 2, but not receptor 1, whereas indomethacin did not alter the expression levels of the vascular endothelial growth factor system. In contrast, ibuprofen significantly induced vascular endothelial growth factor and its receptors 1 and 2 in aortic endothelial cells, whereas indomethacin only induced vascular endothelial growth factor receptor 2.

Conclusion

Our results indicate differential effects of ibuprofen and indomethacin on the expression levels of the vascular endothelial growth factor system in ductus arteriosus endothelial cells. In addition, vessel-specific differences between ductal and aortic endothelial cells were found. Further in vivo studies are needed to elucidate the biological significance of these findings.

Keywords

Ductus arteriosusendothelial cellibuprofenindomethacinVEGF
Type
Original Articles
Information
Cardiology in the Young , Volume 28 , Issue 3 , March 2018 , pp. 432 - 437
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Copyright
© Cambridge University Press 2017 

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