Reduced Macrophage-Dependent Inflammation Improves Endothelin-1–Induced Vascular Injury
Bibliographic record
Abstract
Transgenic mice with endothelium-specific endothelin-1 (ET-1) overexpression exhibit endothelial dysfunction and vascular remodeling, oxidative stress, and inflammation. We previously observed that monocytes/macrophages play a role in angiotensin II, aldosterone, and deoxycorticosterone acetate/salt-induced vascular remodeling, oxidative stress, and inflammation using a model with reduced monocytes/macrophages, the osteopetrotic (Op) mouse, which has a mutation in the macrophage colony stimulating factor (Csf1) gene. However, it is unknown whether monocytes/macrophages are implicated in adverse vascular effects of ET-1. We hypothesized that reduction in monocytes/macrophages would blunt ET-1-induced vascular injury. We performed a study on 4- to 6-month-old male mice with endothelium-specific ET-1 overexpression (eET-1), reduction in CSF1 (Csf1(Op/+)), or both (eET-1/Csf1(Op/+)), and their wild-type littermate control mice. There was no difference in 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/Csf1(Op/+) mice. Media:lumen ratio and media cross-sectional area were ≈1.5-fold greater in eET-1 than in wild-type mice (P<0.05), which was not observed in mice deficient in CSF1. ET-1-induced oxidative stress measured by dihydroethidium staining (P<0.05) and NADPH oxidase activity assessed with lucigenin chemiluminescence (P<0.05) were blunted by CSF1 deficiency. ET-1 caused a 2.5-fold increase in monocyte/macrophage infiltration compared with wild-type mice (P<0.001), which was blunted in the mice deficient in CSF1. Reduction of monocyte/macrophage-dependent inflammation in mice overexpressing ET-1 in endothelium results in reduced vascular remodeling and oxidative stress, providing evidence for a role of monocytes/macrophages and innate immunity in ET-1-induced vascular injury.
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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 | 0.001 | 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) | 0.001 | 0.000 |
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".