Implication of reduced levels of intracellular cAMP in enhanced expression of Gi proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats: cellular mechanisms
Bibliographic record
Abstract
We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibited an increased expression of Gi proteins and hyperproliferation, whereas the levels of cAMP were decreased as compared to WKY control rats. The enhanced levels of endogenous AngII and ET‐1 in VSMC from SHR were shown to contribute to the increased expression of Gi proteins through the transactivation of EGFR and MAP kinase signaling pathways. The present study was undertaken to examine if the decreased levels of intracellular cAMP in VSMC from SHR contribute to the enhanced expression of Gi proteins and hyperproliferation and to explore the underlying signaling pathways. Protein expression was evaluated by Western blot analysis and cell proliferation by thymidine incorporation. Treatment of VSMC from SHR with dbcAMP attenuated the enhanced expression of Gi proteins and the enhanced proliferation to control levels. In addition, the increased phosphorylation of ERK1/2, c‐Src, EGFR and PDGFR in VSMC from SHR was also inhibited by dbcAMP. Furthermore, dbcAMP decreased the enhanced production of superoxide anion and enhanced expression of Nox4, p47 proteins. These results suggest that the decreased levels of intracellular cAMP in VSMC from SHR contribute to the enhanced expression of Gi protein and proliferation through ROS‐mediated EGFR/PDGFR activation and ERK1/2 signaling pathway (Supported by CIHR).
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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".