Abstract 66: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Oxidative Stress and Rho Kinase
Bibliographic record
Abstract
Aldosterone (aldo) plays a role in obesity and cardiovascular diseases, such as hypertension. We previously demonstrated that adipocyte-derived factors regulate vascular function and vascular smooth muscle cells signaling. Moreover, adipocytes express aldosterone synthase (CYP11B2) and produce aldo. The mineralocorticoid receptor (MR), which is responsible for aldo signaling, is also found in these cells, but its role in regulating adipose tissue interactions with the vasculature is unknown. In this study, we investigated mechanisms whether MR activation in adipocytes regulates vascular reactivity. Conditional transgenic mice that overexpress MR in an adipocyte-specific manner were studied. Vascular reactivity of resistance mesenteric arteries to acetylcholine (Ach), sodium nitroprusside and phenylephrine (Phe), in the absence or presence of fat conditioned medium (Fcm) from control and adipocyte overexpressing MR (MROE) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in MROE or control (Ctr) mice. However, exposure of arteries from control mice to Fcm from MROE mice induces endothelial dysfunction (Ach 10 -6 M: 77.5±9.6% no Fcm vs. 49.8±7.5% Fcm, p<0.05), an effect blocked by N-acetyl-cysteine (an antioxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from MROE mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm Ctr vs. 1.7±0.2 mN/mm MROE, p<0.05). Rho Kinase activity, which regulates vascular contraction, is decreased in arteries and adipo tissue from MROE (mesenteric arteries, Ctr: 100±16.2% vs. MROE: 31.1±6.1%, arbitrary units, p<0.01; adipose tissue, Ctr: 100±12.6% vs. MROE: 51.3±9.3%, arbitrary units, p<0.01). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, through redox-sensitive pathways and activation of Rho kinase. Our study identifies novel mechanisms linking vascular/adipose tissue biology and aldo/MR activation, which may be particularly important in vascular dysfunction associated with hypertension and hyperaldosteronism.
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 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".