The expression of VEGF and its receptors in the human ductus arteriosus.
Programmed proliferative degeneration of the human fetal ductus arteriosus (DA) preceding definite postnatal closure has a large developmental variability and is controlled by several signaling pathways. Among these vascular endothelial growth factor (VEGF) and its receptors (VEGF-Rs) play an important role. Until now, gestational age dependent expression of VEGF and its receptors has not been investigated in a large number of human DA tissue specimens. We examined protein expression of VEGF and the three VEGF-Rs immunohistochemically in 63 human fetal autopsy DA specimens of 11-38 wk gestation. Specimens were classified into different maturity stages according to their histologic appearance. VEGF and VEGF-Rs-staining was detected in all maturity stages. VEGF-staining was localized perinuclearly in all vascular layers and did not change during development. VEGF-R1 and VEGF-R3 expression was marked in the endothelium in early maturity stages and decreased during development. In contrast, -R2 predominated in the media in later developmental stages. Our results emphasize the importance of VEGF as a mediator during programmed proliferative degeneration of fetal DA and support the hypothesis that VEGF-R1 and VEGF-R3 are required for normal blood vessel development during embryogenesis. In contrast, VEGF-R2 is the predominant receptor in later angiogenic signaling.
Department of Neonatology, Humboldt University, 13353 Berlin, Germany.
Sven C
SC
Weber
Cornelia
C
Rheinlaender
Nanette
N
Sarioglu
Christian
C
Peiser
Mario
M
Rüdiger
Michael
M
Obladen
Petra S
PS
Koehne
D000367:Age Factors; D004373:Ductus Arteriosus / Q000378:metabolism*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D018709:Statistics, Nonparametric; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor