MPS 18-02 ENDOTHELIN-1 OVEREXPRESSION PRESERVES ENDOTHELIAL FUNCTION IN MICE WITH VASCULAR SMOOTH MUSCLE CELL-SPECIFIC DELETION OF PPAR-GAMMA
Bibliographic record
Abstract
Objective: Peroxisome proliferator-activated receptor γ (PPARγ) agonists reduce blood pressure (BP) and vascular injury in hypertensive rodents. Pparγ inactivation in vascular smooth muscle cells (VSMC) using a tamoxifen inducible Cre-Lox system enhanced angiotensin II-induced vascular damage. Transgenic mice overexpressing endothelin (ET)-1 in the endothelium (eET-1) exhibit endothelial dysfunction, increased oxidative stress and inflammation. We hypothesized that inactivation of the Ppar gene in VSMC (smPparγ−/−) will exaggerate ET-1-induced vascular damage. Design and Method: Eleven week-old male control, eET-1, smPparγ−/− and eET-1/smPparγ−/− mice were treated with tamoxifen (1 mg/kg/day, s.c.) for 5 days and sacrificed 4 weeks later. BP was measured by telemetry. Endothelial function and vascular remodeling using pressurized myography, reactive oxygen species (ROS) production by dihydroethidium staining, monocyte/macrophage infiltration by immunofluorescence and mRNA expression by reverse transcription-quantitative PCR were assessed in mesenteric arteries (MA) or perivascular fat (PVAT). Spleen T cell and monocyte profiles were assessed by flow cytometry. Results: Systolic BP was 20 mmHg higher in eET-1 and unaffected by Pparγ inactivation. MA vasorelaxation to acetylcholine was impaired 37% only in smPparγ−/−. Likewise, ET-1-induced contractions were enhanced only in smPparγ−/−. ROS levels were increased 1.7-fold in smPparγ−/− and 2.5-fold in eET-1/smPparγ−/−. Monocyte/macrophage infiltration in PVAT was 2-fold higher in eET-1 and smPparγ−/−, which was further increased 2-fold in eET-1/smPparγ−/−. The percentage of CD11b+ cells was increased 2.3-fold in smPparγ−/− and further increased 1.5-fold in eET-1/smPparγ−/−. The percentage of Ly-6Chi monocytes was increased ∼1.8-fold in eET-1 and smPparγ−/− but not eET-1/smPparγ−/−. The percentage of T regulatory cells was increased 1.5-fold in smPparγ−/− and decreased by 26% in eET-1, which was further decreased by 38% in eET-1/smPparγ−/−. Conclusions: These results suggest that increased ET-1 paradoxically preserves endothelial function in mice with inactivated VSMC Pparγ despite enhanced oxidative stress. Flow cytometry data indicate that infiltrating monocyte/macrophages in these mice might be anti-inflammatory.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| 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) | 0.004 | 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".