Abstract 413: A Dominant Negative Mutant of Plasminogen Activator Inhibitor-1 Does Not Inhibit Intimal Hyperplasia After Balloon Coronary Angioplasty in Pigs
Bibliographic record
Abstract
Background. Plasminogen activator inhibitor 1 (PAI-1) regulates arterial remodeling and intimal hyperplasia after vascular injury. PAI-1-R is a recombinant mutant that completely lacks anti-protease activity yet binds vitronectin (VN) with normal affinity. PAI-1-R inhibits cell migration in vitro and neointima formation in rodents by binding VN and competitively blocking its binding to integrins. Objective and Methods. To determine if PAI-1-R inhibits intimal hyperplasia under experimental conditions highly relevant to human coronary artery disease we performed balloon angioplasty of the left circumflex coronary artery (LCX) of male pigs and administered PAI-1-R by direct coronary infusion immediately after angioplasty and by peripheral intravenous infusion on each of the next two days (5 mg/infusion; total dose 15 mg/pig). Thirteen pigs (weight 24±4.3 kg) received PAI-1-R and 13 pigs (weight 24 ± 4.7 kg) received identical infusions of vehicle control. Animals were euthanized 14 days after angioplasty and neointima formation in the injured LCX was determined by microscopic morphometric analysis. Results. Plasma PAI-1-R concentrations assessed 1 hr after each infusion were 32±18, 89±60, and 59±16 ng/mL, respectively, in PAI-1-R-treated pigs and undetectable in controls. There was no significant difference in LCX neointima formation between PAI-1-R- vs. vehicle-treated pigs (maximal intima thickness 523±47 vs. 581±49 μm, p=0.41; intima area/media area normalized to media rupture length 3.7±0.3 vs 3.8±0.3, p=0.8). Conclusion. Short-term, bolus infusions of a dominant negative form of PAI-1 do not significantly inhibit neointima formation in pigs after coronary angioplasty. These results contrast with rodent data and suggest that alternative strategies that achieve higher concentrations of PAI-1-R at vascular injury sites will be required to assess the efficacy of this strategy under clinically relevant conditions.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".