Abstract 16822: Endothelial c-Myc Protects the Heart From Pro-Inflammatory Changes During Aging and Atherogenic Stress
Bibliographic record
Abstract
Background: Inflammation plays an important role in cardiac remodeling and occurs in response to risk factors such as aging and high-fat diet (HFD). We have recently reported that c-Myc knockdown in endothelial cells triggers a senescence-associated pro-inflammatory phenotype. We found that c-Myc expression declines in human coronary artery endothelial cells (HCAECs) during replicative senescence and aging. These findings suggest that threshold levels of c-Myc in endothelial cells are required to protect the heart. Here we investigated the impact of endothelial c-Myc in the heart during aging and exposure to HFD using a transgenic mouse model with endothelial-specific c-Myc overexpression. Methods and Results: Gene expression profiling and pathway analysis of young (2-month) and old (10-month) mice showed that endothelial c-Myc overexpression has a protective effect, increasing the expression of genes that prevent cardiac hypertrophy such as Rgs2, Braf and Ppargc1a and reducing inflammatory mediators such as S100a9 and Ptx3. We validated the expression of inflammatory markers IL-1β, Cxcl1 and TGF-β2 by qPCR and found that in aged group, their expression was downregulated in transgenic mice by 2.46 (p<0.002), 2.92 (p<0.001) and 1.85 (p<0.001) fold, respectively, relative to control mice. We further explored this novel protective role of c-Myc in the context of HFD using pre-designed Taqman stress array. Results showed significant downregulation of genes involved in oxidative stress (Noxo1, -1.72-fold, p<0.01), autophagy (Tfeb, -1.72-fold, p=0.03) and DNA repair (Bub1b, -1.37-fold, p=0.02) in transgenic mice under control diet. In response to HFD, most stress genes were downregulated in control mice while a specific group was upregulated in transgenic animals, including genes involved in autophagy (Tfeb, 1.39-fold, p=0.06) and antioxidant pathways (Txnrd2, 1.58-fold, p=0.03; Msra, 1.72-fold, p=0.04 and Msrb3, 1.47-fold, p=0.05). Conclusion: Our c-Myc overexpression mouse model exhibits a distinct gene expression pattern that is potentially cardiac protective in response to aging and HFD. Endothelial c-Myc may be essential to protect cardiac tissues under stress conditions.
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 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".