Endothelin‐1 (ET‐1) induces Ca2+‐Calmodulin‐dependent Protein Kinase II α (CaMKII‐α) expression in an ERK1/2‐dependent pathway in vascular smooth muscle cells (VSMC)
Bibliographic record
Abstract
ET‐1 is implicated in the pathogenesis of vascular abnormalities, such as hypertension and atherosclerosis, through the hyperactivation of growth promoting signaling pathways such as ERK1/2 and PKB. We have recently shown that CaMKII‐α, a multifunctional protein kinase plays a critical role in mediating ET‐1‐induced ERK1/2 and PKB signaling as well as proliferative and hypertrophic responses in VSMC. We have also shown that CaMKII‐α level is upregulated in VSMC from spontaneously hypertensive rats (SHR) as compared to normotensive Wistar Kyoto (WKY) rats. Since elevated levels of ET‐1 have been reported in hypertension, we wished to determine if there was a role of ET‐1 in the heightened expression of CaMKII‐α observed in SHR. Therefore, we examined the effect of ET‐1 on CaMKII‐α expression in VMSC. ET‐1 (100nM) increased CaMKII‐α expression in VSMC in a time dependent fashion, peaking at 90 minutes. Pretreatment with actinomycin D and cycloheximide, respective inhibitors of mRNA transcription and protein synthesis, potently inhibited ET‐1‐induced effect on CaMKII‐α. Furthermore, BQ123 and PD98059, two selective pharmacological inhibitors of ET A receptor and MEK pathway, respectively, attenuated ET‐1‐induced CaMKII‐α expression. These data demonstrate that ET‐1 induces CaMKII‐ α expression in VSMC via an ET A receptor‐mediated activation of ERK1/2 pathway in VSMC. (Supported by CIHR grants).
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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) | 0.001 | 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 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".