Abstract 4140451: Loss of Stem Cell Antigen-1 Worsens Aortic Remodeling in Angiotensin II-Induced Hypertension
Bibliographic record
Abstract
Background: Stem cell antigen-1 (Sca-1) marks progenitor cells that contribute to vessel remodeling by differentiating into vascular smooth muscle cells and related myofibroblasts. We previously demonstrated that Sca-1 is required for pro-fibrotic differentiation following arterial injury. Here, in a mouse model of experimental hypertension (HTN), we assessed the requirement for Sca-1 in aortic dysfunction and remodeling. Methods&Results: Male and female mice homozygous for GFP knock-in/Sca-1 knockout (Sca1KI -/- ), heterozygous littermates (Sca1KI +/- ), and control GFP-labeled Sca-1 reporter mice (Sca1GFP), age 12-14-wk, were subjected to angiotensin II-induced HTN (Ang-II 1000 ng/kg/min) by osmotic mini-pump for 28d, or vehicle (0.9% saline). GFP + CD31 - CD45 - cells from Sca1KI -/- , Sca1KI +/-, and Sca1GFP represent progenitor cells with no-, partial-, or normal Sca-1 expression, respectively. Partial- or total loss of Sca-1 expression exacerbated aortic GFP + CD31 - CD45 - cell expansion, compared to Sca1GFP [Sca1KI -/- 32±7-fold change of vehicle vs. Sca1KI +/- 39±9 vs. Sca1GFP 5±1; n=11-13/group; p<0.0001], suggesting disinhibited progenitor responses. Interestingly, Sca1KI -/- mice manifest blunted HTN in response to Ang-II [Sca1KI -/- 130±9 mmHg vs. Sca1KI +/- 159±8 vs. Sca1GFP 160±10; n=6-7/group; p<0.01]. Partial- or total loss of Sca-1 worsened aortic dilation [Sca1KI -/- 1.25±0.06 mm vs. Sca1KI +/- 1.21±0.06 vs. Sca1GFP 1.04±0.05; n=6-7/group; p<0.05], aortic wall thickness [Sca1KI -/- 105±9 μm vs. Sca1KI +/- 136±16 vs. Sca1GFP 82±5; n=6-7/group; p<0.01], adventitial area [Sca1KI -/- 79±13 mm 2 vs. Sca1KI +/- 178±46 vs. Sca1GFP 51±6; n=6-7/group; p<0.01], and aortic aneurysm formation [Sca1KI -/- 6/17 vs. Sca1KI +/- 6/20 vs. Sca1GFP 2/18]. Underlying these differences, in cultured progenitor cells subjected to TGFβ, pro-fibrotic CD44 expression increased 3.4-fold in Sca-1 deficient progenitors vs . wild-type [54±9% vs. 16±2; n=2-3/group]. Concomitantly, stem cell marker PDGFRα expression on these cultured progenitors was reduced [0.4±0.1% vs. 11±1; n=2-3/group], suggesting depletion of progenitors skewed towards a pro-fibrotic lineage. Conclusion: Partial or complete loss of Sca-1 worsens aortic remodeling in Ang-II HTN by increasing progenitor expansion and pro-fibrotic contributions. These data highlight a critical role for vascular Sca-1 expression, which may inform a novel approach to preventing and treating HTN and associated vascular remodeling.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".