A1156 Cardioprotective effects of Apelin-13 on aging- and angiotensin II-mediated adverse myocardial injury and dysfunction in hypertensive mice
Bibliographic record
Abstract
Objectives: The apelin-APJ system and angiotensin (Ang) II-AT1 pathways have emerged as potent regulators of blood pressure and cardiovascular function. However, the interaction between the apelin and Ang system in myocardial injury remains unclear. Methods: The C57/B6 wildtype (WT), apolipoprotein E (ApoE) knockout (KO) and apelinKO mice were randomized to receive either Ang II (1.5 mg.kg-1.d-1) osmotic minipump and /or 100 ug/kg pyr1-apelin-13 for 4 weeks. Results: 1-year aged APLN-/y mice developed increased myocardial hypertrophy and fibrosis with downregulation of ACE2 levels. Importantly, pyr1-apelin-13 reversed Ang II-mediated hypertension, myocardial apoptosis and pathological hypertrophy in both WT and ApoEKO mice. Ang II-induced cardiac fibrosis, dysfunction and altered myocardial ultrastructure were aggravated in the ApoEKO mice which were prevented by pyr1-apelin-13. Importantly, pyr1-apelin-13 attenuated Ang II-mediated pathological effects in ApoE-null hearts associated with increased levels of ACE2 and p-ERK1/2. In cultured neonatal rat cardiomyocytes and cardiofibroblasts, exposure of Ang II decreased ACE2 protein and increased superoxide generation, cellular proliferation and migration, which were rescued by pyr1-apelin-13, Akt and eNOS agonist stimulation. The increased superoxide generation and apoptosis in cultured cardiofibroblasts in response to Ang II were strikingly prevented by pyr1-apelin-13 which was partially reversed by co-treatment with the Akt inhibitor MK2206. Conclusion: Our data provide definitive evidence for cardioprotective roles of pyr1-apelin-13 in aging- and Ang II-mediated pathological remodeling, myocardial fibrosis and dysfunction. Targeting the apelin-APJ pathway represents a novel therapeutic approach against hypertension.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 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) | 0.000 | 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".