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CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
Recording available 2/16-5/2
Recording available 2/16-5/2
AIUM Credit
AIUM Credit
Foundation Awardee
Foundation Awardee
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Abstract Award
Abstract Award
Foundation Awardee
Foundation Awardee

Poster Session 4

Category: Hypertension

Poster Session 4

(1057) Severe Early-Onset Preeclampsia is Associated with Compromised Placental Oxygen Signaling via HIF-1a and Metabolic Dysregulation

Thursday, February 12, 2026
3:30 PM - 5:00 PM  
Objective:
Hypoxia-inducible factor 1 (HIF-1a) is an oxygen-sensitive transcription factor which has previously been found to be upregulated in placentas of preeclampsia (PE) patients, suggesting placental HIF-1a plays a significant role in the pathogenesis of the condition when elevated beyond the first trimester. In this study, we sought to determine why HIF-1a remains elevated in severe, early-onset PE (sEOPE), and how its elevation leads to metabolic dysfunction in the placenta.

Study Design:
Placentas from healthy pregnant control (n=12) and severe, early-onset preeclampsia (sEOPE) (n=13) were taken at the time of delivery and processed for Western blot analysis.

Results:
HIF-1a was significantly elevated in sEOPE placentas. VHL, which degrades HIF-1a, was significantly decreased. Phosphorylated AKT, which stabilizes HIF-1a, was significantly elevated. A decrease in VHL coupled with increased AKT activity provides a possible mechanism for the sustained elevation of placental HIF-1a. We then assessed downstream targets to determine the impact of elevated HIF-1a. Target proteins in glycolysis were significantly elevated. An enzyme critical for B-oxidation was significantly decreased. The master regulator of cellular energy sensing, pAMPK, was significantly elevated, suggesting low cellular energy. Low cellular energy and HIF-1a elevation have both been shown to decrease antioxidant capacity, and likewise, we found significantly reduced GPX4 protein and decreased total GSH. A marker of endothelial dysfunction and decreased angiogenesis was also significantly elevated, providing further evidence of increased cellular dysfunction.

Conclusion:
Severe, early-onset preeclampsia (sEOPE) is known to result from abnormal placentation resulting in compromised placental oxygen signaling, leading to sustained elevation of placental HIF-1a. This elevation results in a shift from oxidative phosphorylation to glycolysis, decreased cellular energy, reduced B-oxidation, and diminished antioxidant capacity. Our results provide compelling evidence for the significance of elevated placental HIF-1a in sEOPE pathogenesis.