Abstract 105: Evidence that Serum Amyloid A Mediates Inflammation and Matrix Degradation in Abdominal Aortas of Angiotensin II--Infused ApoE-/- Mice
Bibliographic record
Abstract
Objectives: Infusion of angiotensin II (AngII) into apoE -/- mice results in abdominal aortic aneurysms (AAA) that exhibit features of human AAA, including medial degradation, inflammation, and rupture. We determined that apoE -/- mice deficient in acute phase serum amyloid A (SAA) are protected from AngII-induced AAA (unpublished data). SAA is thought to orchestrate the inflammatory response to tissue injury by stimulating cytokine induction, inflammatory cell recruitment, and extracellular matrix turnover. In this study we performed in vitro and in vivo studies to test the hypothesis that SAA promotes AAA by augmenting inflammation and matrix degradation in abdominal aortas of AngII-infused mice. Methods and Results: Male apoE -/- mice were infused with 1000 ng/kg/min AngII or saline for 10 days. Abdominal aortas, defined as the 10.4mm region of the aorta immediately above the right superior renal vessel, were analyzed in vivo using a 7T ClinScan MRI and ex vivo by immunohistochemistry and in situ zymography. Vessel wall distensibility was markedly lower in the AngII-infused mouse abdominal aorta (0.54%/mm Hg) compared to saline control (1.07%/mm Hg). Sections of AAA corresponding to regions of lowest distensibility were distinguished by breaks in the elastin lamina that co-localized with intense matrix metalloproteinase (MMP) activity and prominent macrophage and SAA immunoreactivity. In more distensible regions of AAA, there was no evidence of elastin breaks, and MMP activity and macrophage and SAA immunoreactivity were less pronounced. Primary mouse aortic smooth muscle cells (VSMC) were cultured for 3 days and then treated for 8 hours in the presence or absence of 50μg/ml purified mouse SAA. Results from RT-PCR arrays indicated that SAA altered the expression of genes involved in inflammation (52 out 84 analyzed) and extracellular matrix/cell adhesion (24 out of 84 analyzed). Conventional RT-PCR confirmed that SAA induces the expression of Ccl2, MMP9 and MMP13 in mouse aortic VSMCs. Conclusions: SAA stimulates chemokine and MMP expression in VSMC that may lead to macrophage infiltration, medial degradation, and decreased arterial distensibility in AngII-induced AAA. SAA is potentially a useful biomarker and therapeutic target for human AAA.
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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 | 0.001 | 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) | 0.002 | 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".