Abstract 534: Peripheral Artery Disease Increases Platelet Activity and Promotes a Prothrombotic Platelet Phenotype
Bibliographic record
Abstract
Background: Peripheral artery disease (PAD), characterized by lower extremity atherosclerosis, increases the risk of cardiovascular morbidity and mortality. Among their many functions, platelets modulate hemostasis, thrombosis, inflammation, and angiogenesis. Previously, we noted the potent pathogenic role of platelets in PAD. However, how vascular dysfunction impacts the platelet phenotype is not fully understood. Using a mouse model of PAD (hindlimb ischemia), we investigated the platelet phenotype and transcriptome. Methods: Eighteen C57BL/6J mice (10 weeks) underwent femoral artery ligation (HLI) or sham surgery. Platelet activity, P-selectin, JON/A expression, and platelet-leukocyte aggregation, was assessed at day 0, 3, 7, 10, 14, and 21. At day 21, we performed the FeCl3-induced thrombosis model and assessed time to vessel occlusion. To investigate platelet-relevant mechanisms, we induced HLI or sham surgery in 20 mice and collected platelets for RNA sequencing (day 12). Results: Our acute PAD model resulted in >90% drop in blood flow after the procedure with ≈50% recovery at day 21. Following the procedure, platelet activity, defined by PAR4 agonist stimulated P-selectin expression (P=0.001), αIIbβ3 activation (JON/A expression, P=0.002), platelet-neutrophil aggregation (P<0.001) and platelet monocyte aggregation (P=0.047) increased over time in the HLI vs sham group. Mice in the HLI group had faster occlusive carotid thrombosis than the sham group (P=0.026). Comparing the platelet transcriptome in the HLI vs sham group noted 895 differentially expressed transcripts (P<0.05) between groups (516 up-, 79 down-regulated). Pathway analysis between groups demonstrated enrichment of inflammatory pathways, including interleukin-1 mediated signaling (P=0.02), apoptotic process (P=0.02), noncoding RNA processing (P=0.02), and signaling receptor binding (P=0.03). Conclusion: In our murine model of acute PAD, we found increased platelet activity, a proinflammatory platelet transcriptome, and a prothrombotic state. These data highlight the feasibility of the HLI model to further investigate platelet-associated mechanisms that underlie PAD.
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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) | 0.000 | 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) | 0.009 | 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".