Abstract 279: Vascular Aging In Aldosterone Associated Hypertension: Role Of NADPH Oxidase 1
Bibliographic record
Abstract
In hypertension, vascular aging is accelerated leading to heart failure, stroke and renal dysfunction. Cellular and molecular mechanisms of age-associated vascular changes are unclear, but enhanced ROS generation by NADPH oxidases (Nox) and aldosterone (aldo) have been suggested. Nox1 is of particular interest due to increased levels in hypertension. Here, we postulated that aldo plays an important role in vascular aging through Nox1-dependent mechanisms. We examined signalling molecules associated with aging in arteries from 2 experimental models: stroke-prone spontaneously hypertensive rats (SHRSP) rats and Nox1 knockout mice infused with aldo (300 ug/Kg/day). Gene expression was assessed by qPCR and protein levels by immunoblotting. Aldo was measured by ELISA. In SHRSP rats, aging-associated mRNA inflammatory markers, such as RANTES (5- fold), MCP-1 (6-fold) and IL-6 (2-fold); as well as aldo levels (6-fold) and H2AX (marker of aging-associated DNA damage - 1.5-fold) were increased compared with control rats, p<0.05. In mice treated with aldo, JNK (pro-inflammatory - 69%) and p66SHC (pro-senescence - 92%) activation were increased in mesenteric arteries (p<0.05); an effect blunted in vessels from Nox1 KO mice. In parallel studies, vascular smooth muscle cells (VSMCs) from adult and aged control mice, as well as, from adult Nox1 transgenic mice (Nox1 overexpression in VSMCs) were extracted and stimulated with H2O2 and aldo. Basal levels of p66SHC (39%) and OGG-1 (48%), markers of senescence, were increased in VSMCs from aged animals, p<0.05. H2O2 (64%) and aldo (84%) increased p66SHC activation in VSMCs from adult mice to similar levels observed in cells from aged animals (p<0.05). However, aldo effects on p66SHC activation were exacerbated in VSMCs from adult Nox1 transgenic mice. In conclusion, aldosterone may play an important role in the aging-like phenotype in vascular injury associated with hypertension. Such processes may involve Nox1 and redox-sensitive p66Shc signalling.
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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) | 0.010 | 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".