Abstract 1: Hypoxia-Induced Decrease In Cardiac Stem Cell Proliferation Is Associated With Downregulation Of Sirtuin 1
Bibliographic record
Abstract
Background: Myocardial infarction (MI) produces severe hypoxia within regions of the myocardium, resulting in the formation of scar tissue and significant cardiac cell death. Adult hearts contain endogenous cardiac stem cells (CSCs) that have regenerative capacity and participate in myocardial tissue homeostasis and repair post-MI, but are insufficient to promote complete regeneration. The histone deacetylase Sirtuin 1 (SIRT1) likely mediates this hypoxia-induced decrease in regeneration via roles in cell cycle progression and conferring protection from senescence and oxidative damage. Hypothesis: Hypoxia decreases CSC proliferation through reduced SIRT1-mediated deacetylation. Methods and Results: Murine CSCs were grown at room air (21% O2), physiologic (5% O2), and ischemic hypoxic (0.5% O2) conditions for 72 hours. Ischemic hypoxia, but not physiologic, reduced CSC proliferation and DNA synthesis to 25±2.0% (N=3; p<0.05) and 54±7.0% (N=7; p<0.05), respectively, relative to cells grown in room air. SIRT1 protein expression was decreased by 58±10.0% (N=4; p<0.05) and acetylation of Histone H3 Lys9 (2.4-fold; N=5; p<0.05) and p53 Lys379 (1.64-fold; N=4; p<0.05) were increased after 72 hours of growth in 0.5% compared to 21% O2. However, SIRT1 mRNA transcripts remained unchanged. Furthermore, SIRT1 protein was 59±6.0% less stable (N=4; p<0.05) following 8 hours of cyclohexamide treatment in CSCs exposed to 0.5% O2 for 72 hours compared to CSCs exposed to 21% O2. SIRT1 knockdown by RNA interference significantly reduced proliferation of CSCs grown in room air (N=3 and, p<0.05), similar to that observed in un-transfected cells grown under ischemic hypoxia conditions. Conclusion: The decrease in CSC proliferation with hypoxia is in part due to a reduction in SIRT1 protein stability. These results suggest that SIRT1 expression is regulated post-translationally and support a role for SIRT1 in preserving CSC self-renewal under hypoxic conditions.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".