Attenuation of VEGFR-2 Expression by sFlt-1 and Low Oxygen in Human Placenta
Bibliographic record
Abstract
Vascular endothelial growth factor receptor 2 (VEGFR-2), the primary receptor for VEGF, is crucial for normal endothelial function. sFlt-1, a truncated and soluble form of VEGFR-1 which binds and inhibits VEGF, is increased in preeclampsia and is positively regulated by low oxygen. Here, we investigated the effects of sFlt-1 and hypoxia on VEGFR-2 expression and signaling in the human placenta. VEGFR-2 transcript and protein levels were significantly decreased in preeclamptic placentae compared to controls (1.82 and 1.85 fold, respectively). An inverse correlation was observed for VEGFR-2 and sFlt-1 levels in both singleton and twin placentae from patients with preeclampsia. Immunofluorescence analyses revealed co-localization of VEGFR-2 and sFlt-1 in placental vasculature and co-immunoprecipitation analyses confirmed VEGFR-2 and sFlt-1 interaction only in preeclamptic placentae compared to age-matched controls. VEGFR-2 transcript and protein levels from explants cultured in 3% O2 were significantly decreased compared to those incubated at 20% O2 (5.9 and 12.47 fold, respectively). Also, VEGFR-2 transcript levels were significantly decreased in early first trimester placentae (low oxygen environment) compared to late first trimester placentae (2.05 fold). We next explored whether sFlt-1 directly affects VEGFR-2 expression. Treatment of first trimester placental explants with sFlt-1 resulted in significantly decreased levels of VEGFR-2 (2.03 fold) and downstream signaling proteins phospho-ERK (1.60 fold) and phospho-Akt (1.64 fold). Our findings show a novel hypoxia-induced and PE-related down-regulation of VEGFR-2 in the human placenta. sFlt-1, which is known to be increased in hypoxic conditions and PE, directly attenuates VEGFR-2 expression and signaling. A direct interaction between sFlt-1 and VEGFR-2 may represent an important mechanism in VEGFR-2 regulation, inhibition of VEGFR-2-mediated processes in placentation and a novel platform to examine the onset of preeclampsia.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".