New insights on endothelial CaMKII in angiotensin II‐induced hypertension (851.6)
Bibliographic record
Abstract
Angiotensin II‐induced arterial hypertension (AngII‐AH) is associated with an endothelial dysfunction characterized by a Ca2+ dyshomeostasis. Alteration of the delicate balance between reactive oxygen species (ROS) and nitric oxide (NO) then arise. Recent evidences suggest that hypertension stimulates Ca2+ pulsars and CaMKII but the contribution of AngII and the concomitant ROS remains elusive. The aim of this study was to establish a relationship between endothelial Ca2+ pulsars, ROS and CaMKII in AngII‐AH. Acute exposure to high (> 10‐8 M) concentrations of AngII stimulated Ca2+ pulsars and ROS production in high‐speed confocal microscopy. However, lower AngII level (10‐9 M) only increased Ca2+ pulsars frequency, suggesting a role for ROS in the Ca2+ pulsars stimulation. All AngII concentrations induced endothelial CaMKII recruitment within myoendothelial projections. AngII also stimulated NO production, an effect blunted by CaMKII inhibition (KN‐93). Candesartan, an AT1 blocker, partially reduced Ca2+ pulsars stimulation, suggesting roles for both AT receptors. Moreover, an increased in Ca2+ pulsars frequency and ROS production, associated with CaMKII clustering, is also observed in AngII‐AH mice. Our findings shed a new light on hypertension and Ca2+ dyshomeostasis along with their relationships with CaMKII, a key regulator of endothelial function. Grant Funding Source : Supported by CIHR, FRQS, CFI, HSFC and SQHA.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.000 | 0.000 |
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 teacher head, 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".