Abstract 061: Loss of Lymphocyte Adaptor Protein LNK Promotes Acute Aortic Dissection
Bibliographic record
Abstract
Background: Acute aortic dissection (AD) is a life-threatening vascular disease associated with an inflammatory response. A polymorphism in the gene SH2B3 that encodes LNK has been associated with several cardiovascular and autoimmune diseases in humans. LNK is an adaptor protein expressed in hematopoietic and endothelial cells that serves as a brake to cellular proliferation and cytokine production. We hypothesize that loss of LNK promotes AD through an exacerbation of the acute immune response. Methods: Angiotensin II (Ang II) was infused for 3 or 14 days into wild type (WT) and LNK -/- mice. Kaplan-Meier survival curves were generated. After 3 days, the aortic remodeling was accessed by standard histological staining methods and microscopy. The aortic inflammation was characterized by flow cytometry and immunohistochemistry. Results: Ang II infusion induces a rapid and drastic mortality in LNK -/- mice compared to WT mice (66% vs 8%, P <0.001). Necropsies revealed that deaths are due to the development of AD or rupture, localized primarily in the abdominal aorta. Interestingly, during the phase that precedes AD development (day 3 of Ang II infusion), the aortas of LNK -/- mice show significant remodeling with more elastin fragmentation than WT mice (10.5 vs 4.6 breaks, P <0.01) and less adventitial collagen deposition (3.3 vs 4.6 x10 4 μm 2 , P =0.057). Strikingly, collagen qualitative analysis reveals thinner collagen fibers and several areas of disruption and disorganization in the aorta of LNK -/- mice prior to AD development. In parallel, the aorta of LNK -/- mice show an increase in the number of neutrophils and macrophages but not in T cells compared to WT mice. Conclusion: In our model, LNK seems to play a key role in maintaining the aortic wall integrity. Loss of LNK promotes acute inflammation and matrix degradation, leading to the development of AD. Targeting LNK could be a potential therapeutic strategy for the management of aortic dissection.
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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) | 0.004 | 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".