Defining the role of 12-lipoxygenase in regulating platelet-derived extracellular vesicles
Bibliographic record
Abstract
Platelets are traditionally recognized for their role in hemostasis and wound repair, yet they also play a pivotal role in intercellular communication through the release of platelet-derived extracellular vesicles (PMVs). These vesicles contribute to diverse physiological and pathological processes, but the mechanisms governing their biogenesis remain incompletely understood. One candidate regulator is 12-lipoxygenase (12-LO), an enzyme that metabolizes arachidonic acid into the lipid mediator 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE). While 12-LO has been linked to coagulation and neutrophil interactions, its involvement in PMV production has not been clearly defined. In this study, we investigated the role of 12-LO in PMV biogenesis using both human and murine platelet models. Pharmacological inhibition of 12-LO significantly reduced 12(S)-HETE levels and PMV release in activated human platelets. Similarly, platelets from 12-LO-deficient ( Alox12 − / − ) mice exhibited markedly impaired PMV production upon stimulation. Subpopulation analyses revealed agonist-specific effects of 12-LO deficiency on distinct PMV subsets, including mitochondrial-containing vesicles. Importantly, supplementation with exogenous 12(S)-HETE partially restored PMV production in Alox12 − / − platelets, confirming the functional relevance of this lipid mediator. Together, these findings identify 12-LO as a critical regulator of PMV biogenesis and suggest that the 12-LO/12(S)-HETE axis represents a novel therapeutic target in inflammatory and thrombotic disorders.
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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".