Abstract P168: Activated Protein C Inhibits the Development of Myocardial Fibrosis
Bibliographic record
Abstract
Background: Activated Protein C (aPC) is a naturally produced circulating anticoagulant with anti-inflammatory and cytoprotective properties proposed to have beneficial effects on the myocardium. Myocardial fibrosis is a pathophysiologic process evident in many cardiovascular diseases and is believed to directly contribute to eventual organ failure. Using a well-described model of myocardial fibrosis after Angiotensin II (AngII) infusion our aim was to investigate the novel therapeutic function of aPC in the development of fibrosis. Methods: C57Bl/6 mice were continuously infused with AngII (2.0 μ g/kg/min), AngII and aPC (0.4 μ g/kg/min), or saline for a 3d period. Hearts were harvested and processed for analysis. Cellular infiltration and collagen deposition were analyzed using histologic staining. Cellular apoptosis was assessed using a TUNEL assay. Quantitative RT-PCR was used to assess transcript levels of molecular mediators. Results: Infusion of AngII for 3d resulted in multifocal areas of myocardial cellular infiltration associated with significant collagen deposition compared to saline control animals (p≤0.01). The addition of aPC with AngII infusion inhibited this fibrotic response. Co-administration with aPC also inhibited the upregulation of the pro-fibrotic cytokine CTGF expression seen in AngII infused animals (p≤0.01). Apoptosis was also significantly inhibited when aPC was co-administered based on a decrease of in TUNEL positive cells and an increase expression ration of BCL/BAX suggesting an anti-apoptotic effect (p≤0.01), Furthermore, aPC also inhibited the up-regulation of the cell adhesion molecule p-selectin seen in AngII infused animals (p≤0.01). Conclusion: The co-administration of aPC in a model of myocardial fibrosis was able to abrogate completely the fibrotic response. The mechanism of action of aPC appears to be a decreased cellular adhesion molecule expression in the myocardium leading to decreased cellular infiltration and enhanced cellular survival. This data suggests that aPC has the potential as a therapeutic agent in cardiovascular diseases.
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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) | 0.007 | 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".