Abstract 255: Lymphocyte-Specific Adaptor Protein, LNK (SH2B3), Regulates Angiotensin-II Induced Hypertension and Renal/Vascular Inflammation
Bibliographic record
Abstract
LNK, an adaptor protein primarily expressed in hematopoietic cells and endothelial cells, is a negative regulator of cytokine signaling and cell proliferation. A single nucleotide polymorphism in LNK is associated with hypertension, but the mechanism is unknown. Our objective was to determine the effect of LNK on hypertension and inflammation using LNK -/- mice. In response to angiotensin II (Ang II) infusion, LNK -/- mice exhibit elevated systolic BP (SBP) compared to wild type C57Bl/6J mice (WT) as measured by telemetry. At baseline, kidneys from LNK -/- mice exhibit greater levels of total leukocyte and T lymphocyte infiltration, superoxide production, and albuminuria compared to WT mice, and these parameters are further exacerbated by AngII infusion. Aortas from LNK -/- mice exhibit enhanced inflammation, reduced nitric oxide production, and impaired endothelial-dependent relaxation. Bone marrow transplantation studies showed that loss of LNK in hematopoietic cells (not somatic cells) reproduced the phenotype of whole body deletion of LNK with SBP reaching 180 mmHg in response to a subpressor dose of Ang II. Splenic T cells from LNK -/- mice produce elevated levels of interferon-gamma (IFNγ) compared to WT mice. Furthermore, IFNγ -/- mice exhibit blunted hypertension in response to AngII infusion, suggesting that enhanced IFNγ production is at least partly responsible for the aggravated hypertension in LNK -/- mice. Data are summarized in the table (expressed as mean±SEM, n=5-10,* P <0.05 vs WT/Sham, # P <0.05 vs WT/AngII and † P <0.05 vs LNK -/- /Sham). In conclusion, LNK may serve as a novel therapeutic target for hypertension and its associated renovascular disorders.
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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) | 0.006 | 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".