Abstract 244: Cytoprotective Effect of Growth Hormone Releasing Hormone Agonist in Cardiac Stem Cells
Bibliographic record
Abstract
Background: Our group has previously shown that growth hormone releasing hormone receptor agonists (GHRHR-A) improve cardiac performance in heart failure models and reverse remodeling. This effect was associated with an increase in the number of c-kit+ cardiac stem cells (CSCs), suggesting that this agonist might have an effect on these cells. Methods and Results: We investigated the expression of GHRH receptor (GHRHR) in CSCs of different species by flow cytometry analysis. GHRH-R is expressed in 96-98% of CSCs isolated from mouse, rat and porcine. Results were compared to GHRHR expression in HeLa and MCF7, and T47D cell lines, positive and negative controls, respectively. To determine if GHRHR activation can improve CSCs self-renewal, we tested the effect of agonists on porcine CSCs proliferation. The rate of cell division was increased 2-fold with JI38 (GHRHR-A) treatment (3.4 ± 0.7) vs. vehicle control (1.7 ± 0.2) (p<0.05). Pre-treatment of CSCs with the GHRHR antagonist MIA-602, showed a trend toward reversal of the JI38 agonistic effect on proliferation rate (2.2 ± 0.6). These studies were further extended to other GHRHR agonists. In addition to JI38, MR356 and MR409, both of which showed significant increase in CSCs proliferation relative to vehicle control, by 20 ± 5.7%, 37 ± 8.5% and 36 ± 12.2%, respectively (p<0.05). The protective effect of JI38 on porcine CSCs survival was determined under oxidative stress generated by hydrogen peroxide exposure. Pre-treatment of CSCs with JI38 prior to peroxide exposure significantly reduced cell death by 33 ± 2.2% (p<0.02). Similar effects were observed for MR356, which decreased cell death by 12 ± 8.6% (p<0.03). Furthermore, we found that the effect of GHRHR-A on CSCs proliferation was completely reversed by inhibitors of the ERK, PI3K and Akt pathways (p<0.05). Conclusion: These findings confirm for the first time the expression of GHRHR in CSCs. GHRHR-A promotes CSCs proliferation and enhance survival. GHRHR-A effects on CSCs proliferation are mediated through activation of ERK, PI3K and AKT pathways. Accordingly, activation of GHRHR signaling pathways represents a novel therapeutic approach to protect and stimulate endogenous CSC population, promoting cardiac repair.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| 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".