Abstract 60: Reduced Macrophage-dependent Inflammation Improves Endothelial Function and Vascular Remodeling, Oxidative Stress and Inflammation in a Model Of Endothelin-1 Induced Vascular Injury
Bibliographic record
Abstract
Background: Transgenic mice with endothelium specific preproendothelin-1 overexpression (eET-1) exhibit endothelial dysfunction and vascular remodeling, oxidative stress and inflammation independently of hemodynamic effects. However, it is unclear whether vascular inflammation is causally implicated in adverse vascular effects of endothelin-1 (ET-1). We hypothesized that ET-1-induced vascular injury is decreased in a model of reduced macrophage-dependent inflammation, macrophage colony stimulating factor ( mCsf ) mice heterozygote for the osteopetrosis (Op) mutation. Methods and Results: Wild type (WT), eET-1, mCsf Op/+ and eET-1/ mCsf Op/+ mice were studied. There was no difference in tail-cuff systolic blood pressure between groups. Endothelial function and vascular structure were determined on a pressurized myograph. Endothelium-dependent relaxation in response to acetylcholine was similar in eET-1 and eET-1/ mCsf Op/+ . However, in the presence of L-NAME, the magnitude of NO-independent relaxation was greater in eET-1/ mCsf Op/+ compared to eET-1 (72.4±6.7% vs. 40.8±14.4%, P <0.001). Media-to-lumen ratio was greater in eET-1 than WT (0.13±0.01 vs. 0.08±0.01, P <0.01) and unchanged in eET-1/ mCsf Op/+ (0.10±0.01). Media cross-sectional area (μm 2 ) was greater in eET-1 than WT (13521±2106 vs. 8112±381, P <0.05) and unchanged in eET-1/ mCsf Op/+ (8966±1125). Dihydroethidium staining revealed that reactive oxygen species production in aorta was 4-fold higher in eET-1 than WT ( P <0.01) and unchanged in eET-1/mCsf Op/+ . Aortic monocyte/macrophage infiltration was increased 2.6-fold in eET-1 ( P <0.01) and tended to decrease by 45% in eET-1/mCsf Op/+ compared to WT. Conclusion: Reduction of macrophage-dependent inflammation in mice overexpressing ET-1 in endothelium results in improved vascular relaxation and reduced vascular remodeling, oxidative stress and inflammation, providing evidence for a role of macrophages and innate immunity in ET-1-induced vascular damage.
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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 | 0.002 |
| 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".