Examining The Role Of Lysyl Oxidase Enzymes In Atrial Fibrillation Induced By Volume Overload
Bibliographic record
Abstract
Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is linked to atrial electrical and structural remodelling. AF is associated with fibrosis; however, in models imposing atrial stretch, this occurs without changes in collagen transcription, suggesting fibrosis results from collagen stabilization by the Lysyl Oxidases (LOX) family of enzymes. To investigate this relationship, we established a murine aortic regurgitation (AR) model, which induces atrial stretch. AR mice exhibited increased AF susceptibility, decreased atrial refractoriness (AERP), elevated left atria (LA) fibrosis, and macrophage infiltration 2-fold compared to sham mice. LOXL2 inhibitor PXS-5382 reduced AF inducibility, shortened AF duration and attenuated fibrosis without affecting AERP. In contrast, the broader LOX inhibitor PXS-5505 prevented fibrosis without reducing AF inducibility in AR mice but exacerbated AF and fibrosis in sham mice. These results highlight LOXL2's critical role in atrial structural remodelling and AR-induced AF, suggesting it may be a promising therapeutic target for AF.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 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".