Abstract 345: Role Of Vascular Smooth Muscle Cell PPARγ In Aldosterone-induced Vascular Injury
Bibliographic record
Abstract
Background: Peroxisome proliferator activated receptor γ (PPARγ) agonists improve vascular remodeling and endothelial dysfunction in hypertensive rodents and humans. PPARγ activation in vascular smooth muscle cells (VSMC) may be responsible for the vascular protective effects of PPARγ agonists. We previously observed a protective role of VSMC PPARγ in angiotensin II-induced endothelial dysfunction and vascular remodeling. However, it is unknown whether VSMC PPAR plays a similar protective role in adverse vascular effects of aldosterone. We hypothesized that inactivation of the Ppar gene in VSMC (sm Pparγ -/- ) would exaggerate aldosterone-induced vascular injury. Methods: Using a tamoxifen-inducible Cre/loxP system, Pparγ was ablated in VSMC of adult mice. Thirteen week-old control and sm Pparγ -/- mice were infused or not with aldosterone (400 μg/kg/d, SC) for 14 days while receiving 1% NaCl/0.3% KCl in drinking water. Endothelial function and vascular remodeling were assessed in mesenteric arteries (MA) by pressurized myography. Results: Endothelium-dependent relaxation (EDR) responses to acetylcholine were reduced to a similar extent in sm Pparγ -/- and aldosterone-treated control and sm Pparγ -/- mice compared to control mice (E max : 62.5±8.7%, 50.8±8.6% and 56.8±7.9%, respectively, vs 86.4±3.2%, P <0.05). L-NAME, an inhibitor of nitric oxide (NO) synthase, completely blocked EDR in the four groups. Endothelium-independent relaxation response to the NO donor sodium nitroprusside and contractile responses to norepinephrine were similar in the four groups. Preliminary data indicated that aldosterone tended to increase MA stiffness in control mice, as shown by a leftward shift of the stress/strain relationship curve (strain at 140 mmHg, 0.79±0.07 vs 0.89±0.03). Furthermore, Pparγ deletion induced an increase in MA stiffness compared to control, which was not worsened by aldosterone (strain at 140 mmHg, 0.67±0.01, 0.65±0.03, vs 0.89±0.03). Conclusion: These results indicate that either VMSC Pparγ inactivation or aldosterone treatment induce vascular remodeling and endothelial dysfunction, which are not mutually exaggerated. This suggests that PPARγ and aldosterone signal intracellularly through different pathways.
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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) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 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".