Abstract 18704: Late Blockade of Wnt/frizzled Signaling Pathway with UM206 Halts Further Dilatation of the Left Ventricle Following Myocardial Infarction
Bibliographic record
Abstract
Purpose: Current pharmacotherapy cannot stop left ventricular (LV) dilatation that occurs after myocardial infarction (MI). Recently we have shown that in the MI mouse model, LV dilatation can be prevented by pharmacological blockade of Wnt/frizzled signaling with UM206. In these studies UM206 treatment was started immediately after induction of MI. The subject of the current study was to investigate if similar beneficial effects could be obtained with UM206 when treatment was started 3 weeks after the MI induction, when adverse LV dilatation has become manifest. Methods: Swiss male mice were subjected to MI by occlusion of the left anterior descending artery. At 3 weeks post-MI, UM206 administration (Alzet osmotic minipump, 6µg/kg/day) was initiated and animals were sacrificed at 8 weeks post-MI. The results were compared with vehicle (saline)-treated animals (treatment between weeks 3-8) that were also sacrificed at weeks 8 post-MI. Cardiac geometry and function parameters were obtained using 3D-echocardiography (Vevo 2100, Visualsonics, Toronto, Canada). Results: UM206 late treatment had a beneficial effect on both End diastolic volume (EDV, saline: 278 ± 24 mm3, UM206: 202 ± 13 mm3; p<0.01) and End systolic volume (ESV, saline: 250 ± 27 mm3, UM206: 151 ± 15 mm3; p<0.01). Ejection Fraction (EF) was also improved in UM206-treated animals (saline: 11.0 ± 3.2 %, UM206: 23.2 ± 2.6 %; p<0.05), while increased lung weights (an indication of heart failure development) were found in the saline-treated animals only (saline: 319 ± 42 mg, UM206: 214 ± 6 mg, p<0.01). Conclusion: In the MI mouse model, administration of UM206 starting at week 3 post-MI, halts further increases in EDV and ESV while preserving the EF, resulting in improved overall cardiac function and prevention of heart failure development. The results show that pharmacotherapy targeting the Wnt/frizzled signaling can be beneficial in preventing heart failure after MI, even after adverse LV remodeling has been initiated.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 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".