Abstract 13106: Over Expression of Glyoxalase 1 Prevents Chronic Hyperglycemia Induced Explant Derived Cardiac Stem Cell Dysfunction
Bibliographic record
Abstract
Diabetes increases the risk of heart disease and worsens clinical outcomes after myocardial infarction. Given that hyperglycemia promotes the generation of toxic methylglyoxal, the influence of the key detoxification enzyme glyoxalase 1 (Glo1) on chronic hyperglycemia induced explant-derived cardiac stem cell (EDC) dysfunction was investigated. Methods/Results: Sixteen-week old wild type (WT, n=22) or constitutive Glo1 overexpressing (Glo1TG, n=12) mice were studied 2 months after treatment with streptozotocin or vehicle (2.0±0.1 fold increase in glycated hemoglobin, p=0.001 vs vehicle treated mice). Hyperglycemia reduced overall culture yields (86±3% fewer EDCs cultured, p=0.0009) and prolonged population doubling time (30±4% slower growth, p=0.04) while increasing the cellular content of reactive dicarbonyls (27±3% more reactive oxygen species, p=0.0006) within EDCs cultured from WT mice. These intrinsic cell changes reduced the angiogenic potential (74±2% less total endothelial tubule formation, p=0.001) and production of pro-healing exosomes (43±6% fewer exosomes secreted, p=0.04) by hyperglycemic EDCs while promoting EDC senescence (98±28% more senescent EDCs, p=0.03). As compared to transplant of normoglycemic WT EDCs, hyperglycemia reduced the EDC-mediated increases in echocardiographic ejection fraction and dP/dTmax in infarcted normoglycemic WT mice 3 weeks after intra-myocardial injection by 37±8% (p=0.0001) and 25±1% (p=0.001), respectively. In contrast to EDCs cultured from WT hyperglycemic donors, EDCs cultured from Glo1TG mice: 1) decreased the reactive oxygen species content by 46±2% (p=0.0001), 2) increased cell culture yields by 2.2±0.2 fold (p=0.0004) and 3) boosted echocardiographic left ventricular ejection fraction by 27±7% (p=0.0001) while increasing dP/dTmax by 21±4% (p=0.007). Conclusions: Chronic hyperglycemia decreases the regenerative performance of EDCs. Over-expression of Glo1 reduces dicarbonyl stress and prevents chronic hyperglycemia-induced EDC dysfunction.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".