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Abstract
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<h5 class="section-title" id="d2853194e141">Introduction:</h5>
<p id="P6">Fetoplacental angiogenesis plays a vital role in pregnancy outcome. Vascular
endothelial
growth factor A (VEGFA) is one major regulator of angiogenesis. It primarily binds
to FMS-like tyrosine kinase (FLT1) and kinase insert domain receptor (KDR). In most
vascular beds, KDR appears to be the main mediator of angiogenesis. However, the role
of both receptors within the human placenta remains unknown.
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<h5 class="section-title" id="d2853194e146">Methods:</h5>
<p id="P7">Human fetoplacental ECs were isolated/cultured from placentas of full-term,
uncomplicated
pregnancies after scheduled Cesarean section. Cells were subjected to RNA interference
of either FLT1 or KDR followed by MTT, wound scratch, and tube formation assays. ECs
were serum-starved after RNA interference and treated with VEGFA (60 ng/ml), then
subjected to western blot to investigate FLT1 or KDR-mediated signaling. All experiments
were performed in triplicate utilizing ECs from at least three separate subjects.
One-way ANOVA with Tukey post-hoc testing was utilized for statistical analysis.
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<h5 class="section-title" id="d2853194e151">Results:</h5>
<p id="P8">Significant knock-down of FLT1 and KDR was confirmed by qPCR (p<0.01)
and WB (p<0.0001).
KDR knock-down decreased EC metabolic activity (p<0.01), and FLT1 ablation unexpectedly
increased EC proliferation (p<0.01). There was no difference in apoptosis regardless
of FLT-1 or KDR knock-down. FLT1 knock-down significantly impaired wound scratch closure
(p<0.0001) and tube formation (p<0.001). Surprisingly, KDR effects on EC metabolism
had no effect on migration, although KDR was important in VEGFA-stimulated Akt and
ERK activation. In contrast, FLT1 effects on EC motility were Akt and ERK-independent.
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<h5 class="section-title" id="d2853194e156">Conclusion:</h5>
<p id="P9">Human fetoplacental EC migration is primarily regulated by FLT1 but not
KDR.</p>
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