Abstract P104: Activation of Endoplasmic Reticulum Stress and Thrombospondin-1 Anti-Angiogenic Mechanisms in Placentas of Hypertensive Mice
Bibliographic record
Abstract
Background: Thrombospondin-1 (Thbs1) is an anti-angiogenic focal adhesion glycoprotein. It binds to receptors CD36, LRP1 and CD47 activating anti-proliferative and anti-migratory mechanisms. Pre-eclampsia (PE) is characterized by poor placenta perfusion and angiogenesis, which is stimulated by oxidant and endoplasmic reticulum (ER) stresses contributing to placental insufficiency. ER stress has also been linked to Thbs1 anti-angiogenic actions. However, whether this mechanism is active in PE is unclear. Our aim was to describe ER stress and Thbs1 regulation in placental tissues and endothelial cells in a genetic mice model of chronic maternal hypertension and superposed pre-eclampsia. Methods and Results: Placentas (n=8/group) were collected at 18.5 gestational days from transgenic mice overexpressing human renin and angiotensinogen versus controls (C57BL/6). CD31+ endothelial cells were isolated from placental tissues by magnetic separation. ER stress proteins IRE1a and calreticulin (CLR), as well as Thbs1 and receptors expressions were measured by western blot in placental tissues. CLR and Thbs1 localization in endothelial cells was assessed by immunofluorescence. Data are presented as average±SD. Our results show that IRE1a expression was increased in placentas of hypertensive mice (54±24% P=.05) while CLR was not different. However, in endothelial cells, CLR was shown mobilized from the ER compartment towards the membrane in cells of hypertensive pregnancies or in those exposed to hypoxia. Thbs1 (122±51% P=.03) and receptors CD47 (51±21% P=.03) and LRP1 (58±25% P=.04) were more expressed in placentas of hypertensive pregnancies versus controls, while CD36 was not different. The treatment of endothelial cells of hypertensive pregnancies with a Thbs1 inhibitor, LSKL, has significantly enhanced their angiogenic capacity allowing cells to form closed tubes on matrigel in comparison with the lack of closed tubes in untreated cells. Conclusion: Our results described an ER stress state and Thbs1 upregulation in placental tissue and endothelial cells of hypertensive pregnancy. Our findings suggest an important anti-angiogenic role of the Thbs1 mechanism in placentas of hypertensive mice.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".