Extracellular Granzyme B: a key player in aneurysm pathogenesis (P3072)
Bibliographic record
Abstract
Abstract Granzyme B (GZMB) is a pro-apoptotic protease that is released by cytotoxic immune cells and internalized by target cells in a perforin-dependent manner. However, GZMB contributes to aortic aneurysm pathogenesis through a perforin-independent, extracellular process involving extracellular matrix proteolysis. In vitro and in vivo studies have identified decorin, a key regulator of collagen organization, fibrillogenesis and collagen tensile strength, as a GZMB substrate. We hypothesized that GZMB contributes to aortic aneurysm through the degradation of decorin leading to reduced collagen organization and tensile strength resulting in aortic rupture. To induce aneurysm, apoE-/- mice were implanted with osmotic minipumps that constitutively released angiotensin II. Mice were injected with the GZMB inhibitors, serpin A3N or anti-GZMB neutralizing antibody. A dose-dependent reduction in the frequency of aneurysm rupture was observed in mice that received inhibitor. Reduced GZMB and decorin proteolysis were observed in inhibitor-treated mice. Adventitial collagen from serpin-treated mice exhibited higher fibre density and reduced fibril size irregularity. GZMB was also elevated in human aortic aneurysm. GzmB was expressed in lymphocytes in the intraluminal thrombus and in mast cells in the aneurismal aortic adventitia. In summary, extracellular GZMB contributes to decorin degradation resulting in reduced collagen organization and loss of aortic wall integrity leading to aneurysm.
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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) | 0.000 | 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 | 0.001 |
| 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 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".