Abstract P303: Endothelin Modulates Local Complement Activation in Placental Ischemia-induced Hypertension
Bibliographic record
Abstract
Preeclampsia is characterized by hypertension, reduced placental perfusion, intrauterine growth restriction and increased activation of complement, part of innate immunity. Using the Reduced Uterine Perfusion Pressure (RUPP) model of placental ischemia-induced hypertension in rat, our previous work demonstrated the importance of complement activation in mediating maternal hypertension. Previous studies also demonstrated endothelin A receptor (ET A ) plays a significant role in RUPP-induced hypertension, and RUPP-induced systemic complement activation occurs even with ET A antagonism with atrasentan (ATR). To further probe mechanistic connections between complement and endothelin, we hypothesized that ET A regulates local complement activation (C3 deposition). Dams received drinking water with 50 or 75 ug/ml ATR from gestation day (GD)13-19 corresponding to estimated average 5.5-6.6 and 8.0-9.3 mg/kg/day, respectively. On GD14 rats underwent Sham or RUPP surgery with clip placement on abdominal aorta and uterine arteries to decrease placental perfusion. As previously reported, RUPP increased mean arterial pressure (MAP) compared to Sham, and ATR attenuated RUPP-induced hypertension but not RUPP-induced placental C3 deposition (immunohistochemistry). Importantly, in Sham animals ATR increased C3 deposition and ATR 75 markedly decreased message for membrane bound placental complement regulators Crry, CD55 and CD59 that normally control complement activation. These data suggest that endothelin binding ET A modulates endogenous complement regulators to influence and prevent excess pathological complement activation in placenta during pregnancy.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".