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Abstract 12891: Loss of Stem Cell Antigen-1 Worsens Vessel Remodeling

2021· article· en· W3215086092 on OpenAlexaff
Tao Wang, Abdul Momen, Felix Chiu, Faisal J. Alibhai, Ren‐Ke Li, Clinton S. Robbins, Mansoor Husain

Bibliographic record

VenueCirculation · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAngiogenesis and VEGF in Cancer
Canadian institutionsUniversity Health NetworkUniversity of Toronto
Fundersnot available
KeywordsAdventitiaNeointimaMedicineMasson's trichrome stainMyofibroblastPathologyStem cellTrichromeProgenitor cellIntimal hyperplasiaInternal medicineH&E stainStainingFibrosisSmooth muscleBiologyRestenosis

Abstract

fetched live from OpenAlex

Background: Stem cell antigen-1 (Sca-1)-expressing progenitor cells contribute to vessel remodeling by differentiating into vascular smooth muscle cells and related myofibroblast-like progeny. However, the functional role for Sca-1 expression in vessel remodeling has not been examined. Here, we assessed the requirement for vascular Sca-1 using a mouse model of Sca-1 deficiency. Methods & Results: Male and female Sca-1-deficient mice (Sca1KO) and C57BL/6N wild-type mice (WT) controls, aged 12-14-wk, were subjected to wire denudation injury of the left common carotid artery. Sca1KO displayed larger neointima at 14d post-injury [35±3mm 2 vs. 25±3mm 2 , p<0.05, n=11-12/group], and more adventitial matrix at 8d [87±3mm 2 vs. 58±4mm 2 , p<0.001, n=9-11/group] and 14d post-injury [109±10mm 2 vs. 51±11mm 2 , p<0.01, n=11-12/group] by Masson’s trichrome staining. Underlying these differences, cell numbers per cross-section were increased in adventitia at 8d [649±27 vs. 435±30, p<0.001, n=9-11/group] and 14d post-injury [778±45 vs. 485±47, p<0.001, n=11-12/group]. Non-leukocyte proliferation by CD45 - Ki67 + staining was increased 1.8-fold in neointima [p<0.01, n=9-11/group] and 1.4-fold in adventitia [p<0.05, n=9-11/group] at 8d post-injury in Sca1KO vs. WT. Cell-type analyses of Sca1KO vs. WT revealed increased pro-fibrotic vimentin + cell proportions at 8d [1.4-fold in neointima, p<0.05; 2.5-fold in media, p<0.001; 1.8-fold in adventitia, p<0.001; n=9-11/group] and 14d post-injury [1.5-fold in neointima, p<0.05; 1.8-fold in media, p<0.05; 1.9-fold in adventitia, p<0.001; n=11-12/group]. CD45 + leukocyte proportions were increased 1.5-fold in neointima [p<0.01, n=9-11/group] and 1.4-fold in adventitia [p<0.01, n=9-11/group] at 8d post-injury, which was also increased 1.5-fold in adventitia by 14d [p<0.01, n=11-12/group]. Conclusion: Taken together, our findings suggest that the loss of Sca-1 worsens remodeling by disinhibiting proliferative, pro-fibrotic, and immune responses to injury, demonstrating a critical role for vascular Sca-1 expression, which may inform novel strategies for the prevention and treatment of vessel remodeling.

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 imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Other · Consensus signal: none
Teacher disagreement score0.008
Threshold uncertainty score0.028

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0080.001

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.

Opus teacher head0.021
GPT teacher head0.256
Teacher spread0.235 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreOther

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".

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Citations0
Published2021
Admission routes1
Has abstractyes

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