Abstract 138: Altered Vascular Reactivity in Mice Overexpressing Adipocyte Mineralocorticoid Receptors - Role of Rho Kinase.
Bibliographic record
Abstract
Aldosterone (aldo) plays a role in cardiovascular diseases, including hypertension and obesity. We previously demonstrated that adipocyte-derived factors regulate vascular function and cell signaling in cultured vascular smooth muscle cells. Moreover, adipocytes are able to produce aldo, which influences vascular reactivity. Plasma levels of aldo are positively correlated with obesity and hypertension. However, the pathophysiological role of aldo and mineralocorticoid receptors (MR) in adipose tissue and its interactions with the vasculature remains elusive. In our study, we investigated molecular mechanisms whereby activation of MR, in adipocytes, leads to release of vascular reactive factors and regulation of vascular tone, using a conditional transgenic mouse model that overexpresses MR only in the adipocytes. 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 (DT) mice, was performed by myography. In basal conditions, endothelial dysfunction was not observed in DT or control mice. However, in the presence of Fcm from DT mice, relaxation to Ach was impaired in control mice (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 (anti-oxidant) (Ach 10 -6 M: 82.2±6.6%). Resistance arteries from DT mice had decreased Phe-induced contraction, compared to control mice (Phe 10 -5 M: 2.7±0.2 mN/mm CT vs. 1.7±0.2 mN/mm DT, p<0.05). Phosphorylation of ezrin, a marker of Rho kinase activation, measured by immunoblotting, was decreased in white and brown adipose tissues of DT (CT: 3.1±0.7 vs. DT: 0.6±0.1, arbitrary units, p<0.05). In conclusion, MR in adipocytes may play an important role in the regulation of vascular function, and may be involved in vascular oxidative stress. MR in adipocytes is also important to the anti-contractile properties of the adipose tissue through downregulation of Rho kinase signaling. Our study identiy novel mechanisms linking vascular and adipose biology through adipocyte MRs.
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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) | 0.002 | 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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".