Overexpression of Egr‐1 contributes to the enhanced expression of Giα proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats
Bibliographic record
Abstract
Early growth response, Egr‐1, is known to activate the expression of several genes implicated in the development of vascular dysfunction. Earlier studies have shown that angiotensin II (Ang II) enhances the expression of Egr‐1 and Giα proteins in vascular smooth muscle cells (VSMC). In addition, the role of enhanced levels of endogenous Ang II has been shown to contribute to the enhanced expression of Giα proteins in spontaneously hypertensive rats (SHR). The present study was therefore undertaken to examine if VSMC from SHR also exhibit enhanced expression of Egr‐1 proteins and explore its role and underlying mechanisms in the hyperproliferation of VSMC in SHR. The levels of Egr‐1 proteins in VSMC from SHR started increasing at 2 weeks as compared to their normotensive control, WKY (Wistar‐Kyoto rats) and at 12 weeks, the levels of Egr‐1 proteins were increased significantly by 80%. The enhanced levels of Egr‐1 proteins were restored to control levels by losartan (an AT 1 receptor antagonist), BQ123 (an ET A receptor antagonist), BQ788 (an ET B receptor antagonist), as well as by antioxidants, such as N‐acetyl‐L‐cysteine (NAC) and diphenyleneiodonium (DPI) but not by PD123319 (an AT 2 receptor antagonist). In addition, pharmacological inhibitors of platelet‐derived growth factor (PDGF), insulin‐like growth factor (IGF) and epidermal growth factor (EGF) receptors also inhibited the overexpression of Egr‐1 proteins in VSMC from SHR. Furthermore, the enhanced expression of Egr‐1 proteins was attenuated by PD098059, an inhibitor of mitogen‐activated protein kinase (MAPK), but not by wortmannin, an inhibitor of phosphatidylinositol‐3‐kinase (PI‐3‐K). VSMC from SHR exhibit hyperproliferation which was attenuated by knocking down Egr‐1 by siRNA. In addition, siRNA of Egr‐1 also inhibited the overexpression of Giα‐2 and Giα‐3 proteins, as well as cell cycle proteins, including cyclin D1, cyclin E, cyclin dependent kinase 4 (Cdk4), Cdk2 and phosphorylated retinoblastoma protein (pRb). These results suggest that VSMC from SHR exhibit an overexpression of Egr‐1 proteins, which is attributed to the enhanced levels of endogenous Ang II and ET‐1, oxidative stress, growth factor receptors and MAPK and that the overexpression of Egr‐1, through the enhanced expression of Giα and cell cycle proteins, contributes to the hyperproliferation of VSMC from SHR. Support or Funding Information Grant from CIHR This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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) | 0.001 | 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) | 0.002 | 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".