Abstract 19017: Sex Differences in Severe Pulmonary Arterial Hypertension Produced by SU5416 in a Colony of “Hyper-responsive” Sprague Dawley Rats
Bibliographic record
Abstract
Introduction: Our lab has identified a sub-strain of Sprague Dawley (SD) rats from Charles River Labs, obtained from a specific colony housed at a Canadian facility (Sherbrooke, Quebec), which develop severe progressive PAH in response to single injection of SU5416 (SU), a VEGFR2 antagonist, even in absence of chronic hypoxia (CH). This trait appears to due to the presence of unique genetic modifiers found only in this colony. Interestingly, there was a strong sex difference with >70% of males and only <30% of females showing the SU hyper-responsive (HR) phenotype. The purpose of the project was to explore the mechanisms contributing to sex related differences in response to SU alone in a hyper-responsive sub-strain of SD rats. Hypothesis: Sex dependent differences in the HR phenotype are due to the protective effects of female sex hormones, reducing the susceptibility to PAH in response to VEGFR2 inhibition. Methods and Results: Male and female rats were injected with SU (20mg/kg, sc) or vehicle. Right ventricular systolic pressure (RVSP) was measured at four and seven weeks after SU injection. In male SD rats, 72% (13 of 18) of rats exhibited an HR phenotype in response to SU with mean RVSP of 97±18 mmHg in absence of CH; whereas only 27% (7 of 26) of the female rats were responsive to SU alone. We studied the SU responsiveness in the oophorectomized female rats to investigate the role of female sex hormones in the sex-specific HR phenotype. Interestingly, the proportion of HR animals increased drastically in oophorectomized female rats to 71% (10 of 14), compared to non-operated female rats (33%, 4 of 12). Moreover, estradiol replacement completely abrogated the HR phenotype in both male rats and oophorectomized female rats. Conclusion: These data support a role of female sex hormones in modulating the development of severe PAH in response to SU alone in a unique colony of SD rats that exhibit increased sensitivity to VEGFR2 blockade. The HR SD rat colony model exhibits exquisite sensitivity to estrogen and thus provides a unique opportunity to further define the complex interactions between hormonal and genetic modifiers in the development of PAH.
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 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".