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Sallmon, H; Akanbi, S; Weber, SC; Gratopp, A; Rheinländer, C; Koehne, P.
Ibuprofen and indomethacin differentially regulate vascular endothelial growth factor and its receptors in ductus arteriosus endothelial cells.
Cardiol Young. 2018; 28(3):432-437 Doi: 10.1017/S1047951117002311
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Sallmon Hannes
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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.
Find related publications in this database (using NLM MeSH Indexing)
Animals - administration & dosage
Aorta - cytology, drug effects
Cell Culture Techniques - administration & dosage
Cyclooxygenase Inhibitors - pharmacology
Ductus Arteriosus - cytology, drug effects
Endothelial Cells - drug effects, metabolism
Female - administration & dosage
Fetus - administration & dosage
Fluorescent Antibody Technique - administration & dosage
Ibuprofen - pharmacology
Indomethacin - pharmacology
RNA, Messenger - analysis
Rats - administration & dosage
Rats, Wistar - administration & dosage
Vascular Endothelial Growth Factors - metabolism

Find related publications in this database (Keywords)
Ductus arteriosus
endothelial cell
ibuprofen
indomethacin
VEGF
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