Abstract 12568: Angptl2 is Essential for Aortic Valve Development in Mice
Bibliographic record
Abstract
Introduction: Angiopoietin-like 2 (Angptl2) is a pro-inflammatory anti-apoptotic protein, secreted by senescent cells. Angptl2 also contributes to maintain tissue homeostasis, and we previously reported that adult Angptl2-knockdown (KD) mice exhibit spontaneous Aortic Valve (AoV) stenosis with thickened leaflets compared to wild-type (WT) littermates. It is unknown whether and how Angptl2 contributes to AoV development. Hypothesis: Angptl2 is expressed in the AoV at the embryonic stage and is essential for its development, by contributing to programmed apoptosis/senescence and proliferation occurring during organogenesis. Methods: Embryonic hearts aged 14.5 (E14.5) and 18 days (E18) of Angptl2 -KD and WT mice were dissected. Protein expression (immunofluorescence) and leaflets/hinges thickness of AoV (hematoxylin & eosin) were quantified in histological sections. Data are mean±SEM of n embryos. Results: Compared to WT mice, in AoV leaflets from Angptl2 -KD mice at E14.5, we observed a decrease in apoptotic cells (determined by TUNEL;-47%, p<0.05, n=4), mostly in Valve Interstitial Cells (VICs), a decreased number of Valve Endothelial Cells (VECs) expressing the senescence marker p21 (-48%, p<0.05, n=4), together with a trend towards an increased cell proliferation (Ki67; +396%, p=0.13, n≥6). In turn, a premature thickening of both the leaflets (from 73±18 to 91±33μm, p<0.05, n≥8) and the hinges (from 38±10 to 49±20μm, p<0.01, n≥8) of the valves was measured in Angptl2 -KD mice at E18. Concomitantly, Angptl2 is dynamically expressed during AoV development in WT mice: at E14.5, Angptl2 is expressed in all cell types, suggesting that it could effectively contribute to regulate apoptosis/senescence in both VICs and VECs. At E18, Angptl2 expression in WT mice is restricted to VICs at the border of the leaflet, where the mechanical stress is high, a pattern also observed in adult WT mice. Conclusions: Knockdown of Angptl2 is deleterious to AoV development by disturbing the fine balance between embryonic cell apoptosis/senescence and proliferation, which is essential to adequate AoV maturation; this unbalance progresses to severe AoV stenosis in adult mice. Angptl2 -KD is a new mouse model of spontaneous AoV stenosis, a disease in high medical needs.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.013 | 0.004 |
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".