Abstract 630: Differential Renal And Cardiac Effects Of Nox4 In Chronic Angiotensin II-Dependent Hypertension
Bibliographic record
Abstract
A role for Nox4 in hypertension remains in question. Both protective and injurious Nox4-dependent renal and cardiovascular effects have been reported. We assessed whether gene-targeted Nox4 deficiency (Nox4 -/- mice) could affect development of hypertension, cardiac hypertrophy and renal function in a model of chronic angiotensin II (AngII)-dependent hypertension. We studied mice transgenic for active human renin under the control of the transthyretin promoter (LinA3 mice); these mice develop hypertension over the course of their lifespan. Four genotypes of mice were generated: Wild-type (WT), LinA3, Nox4 -/- , and LinA3/Nox4 -/- . Nox4-deficiency prevented the development of hypertension (LinA3: 154 vs LinA3/Nox4 -/- : 135 mmHg) and cardiac hypertrophy (LinA3: 2.55 vs LinA3/Nox4 -/- : 1.73 mg/g) observed in LinA3 mice ( P <0.05) and was associated with reduced systemic oxidative stress (Plasma TBARS - LinA3: 2.13 vs LinA3/Nox4 -/- : 1.71 mM) . Furthermore, cardiac collagen content was decreased in Nox4 -/- versus LinA3 mice. While Nox4 deficiency attenuated hypertension in LinA3 mice, it yielded detrimental effects on renal function. Specifically, albumin-to-creatinine ratio was significantly elevated in LinA3/Nox4 -/- mice compared with LinA3, Nox4 -/- and WT littermates. LinA3 mice showed evidence of mild segmental glomerulosclerosis. LinA3/Nox4 -/- mice developed severe renal lesions including increased glomerular tuft to fibrotic area, global glomerulosclerosis with numerous foci containing perivascular and peritubular monocyte/macrophage cell infiltration. These findings demonstrate that while global Nox4 deletion may be protective for cardiac pathology and hypertension it is conducive to renal injury in a model of chronic AngII-mediated hypertension. Our data indicate tissue-specific effects of Nox4, which may explain divergent renal and cardiac Nox4 actions in Ang II-dependent hypertension.
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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) | 0.000 | 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".