Elevation of intracellular levels of nitric oxide in SHR attenuates hyperproliferation of vascular smooth muscle cells through the inhibition of AT1 receptor expression and c-Src/growth factor receptor signaling pathways
Bibliographic record
Abstract
Abstract We previously showed that decreased levels of intracellular nitric oxide (NO) contribute to the hyperproliferation of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). The present study investigates if elevation of intracellular levels of NO by in vivo treatment of SHR with NO donor, sodium nitroprusside (SNP) that was shown to attenuate hypertension could attenuate the hyperproliferation of VSMC and identify the molecular mechanisms. Intraperitoneal injection of SNP (0.5 mg/kg BW) into 8-week-old SHR and WKY rats twice a week for two weeks increased significantly the intracellular levels of NO in aortic VSMC and resulted in the attenuation of hyperproliferation of VSMC from SHR to control levels. The antiproliferative effect of SNP was associated with the restoration of the overexpression of cell cycle proteins, cyclins D1, E, Cdk2, Cdk4, phosphorylated pRB and decreased expression of Cdk inhibitors p21 Cip1 and p27 Kip1 towards control levels. In addition, SNP treatment also attenuated the overexpression of angiotensin II receptor type 1 (AT1) receptor, phosphorylation of c-Src, EGF-R, PDGF-R, IGF-IR and ERK1/2 in VSMC from SHR to control levels. These results suggest that the augmentation of intracellular levels of NO elicits antiproliferative effect that may be mediated through its ability to inhibit the enhanced expression of AT1 receptor, activation of c- Src, growth factor receptors and MAP kinase signaling and overexpression of cell cycle proteins.
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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".