Role of Stem Cell Antigen-1 Expressing Cells in Right Ventricular Remodelling in Chronic Hypoxia-induced Pulmonary Hypertension
Bibliographic record
Abstract
Abstract Rationale: Recent evidence suggests that most stem cell antigen-1 expressing cells (Sca-1+ cells) are the tissue-resident endothelial stem/progenitor cells and may contribute to angiogenesis during cardiac remodelling. Importantly, adequate angiogenic response has been shown to be critical for right ventricular (RV) adaptation and survival in pulmonary hypertension (PH). Therefore, in this study, we examined the relevance of Sca-1+ cells in RV remodelling using the rat chronic hypoxia model. Methods: Heart samples from male and female Sprague Dawley and Fischer CDF rats were collected and digested to obtain single cell suspension. Cells were stained with antibodies against Sca-1 and CD31 (endothelial cell marker) and analysed using flow cytometry. Sca-1+ cells from the heart were isolated using magnetic sorting and lectin binding and acetylated low-density lipoprotein (ac-LDL) uptake were assessed. To assess the effect of RV pressure overload, male and female Fischer CDF rats were subjected to 3 weeks of hypoxia (10% O2) and cardiac structure and function were assessed using echocardiography. Heart samples were collected, and Fulton index was measured to assess RV hypertrophy. Immunofluorescence straining of RV and LV samples was performed to assess abundance and localization of Sca-1+ cells were quantified using immunofluorescence staining of the heart sections. Results: Most (>95%) of Sca-1+ cells in the heart expressed CD31 and demonstrate lectin binding and ac-LDL uptake. In response to hypoxia, RV systolic pressure was increased significantly in male and female rats (64.4 and 58.2 mmHg) compared to controls (29.3 and 28 mmHg). Significant elevation in the RV hypertrophy was observed in male (47%) and female (45.6%) rats compered to controls (27.6 and 26%, respectively). Importantly, these rats demonstrated adaptive RV remodelling and preserved RV function in response to chronic hypoxia as indicated by similar RV fractional shortening and cardiac index in hypoxia treated rats compared to controls. Adaptive RV remodelling in hypoxia treated rats was associated with an increase in the abundance of Sca-1+ cells in the RV of male (14.4%) and female (14.6%) rats compared to control rats (7.98% and 12.2%, respectively). Immunofluorescence staining demonstrated localization of Sca-1+ cells to vascular endothelium in the RV. Conclusions: The cardiac Sca-1+ cells in the heart may be the resident endothelial stem/progenitor cells may contribute to angiogenesis and RV adaptation.
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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) | 0.000 | 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) | 0.001 | 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 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".