Abstract 196: Cardiotrophin-1 Promotes Physiologic Cardiac Hypertrophy
Bibliographic record
Abstract
The post-natal heart retains a remarkable adaptive capacity, which matches growth of the myocardium to increased physical demands. The beneficial form of myocardial growth is referred to as physiologic hypertrophy, and derives from a compensatory response to conditions that require increased blood volumes such as pregnancy and chronic exercise training. Despite the clear benefits associated with this form of adaptation, the molecular mechanism(s) that initiate or sustain such cardiac remodeling remain obscure. As such, identification of factors that promote physiologic hypertrophy will be of considerable interest to both cardiac biologists and clinicians. Here, we have begun to explore the role of the cytokine, cardiotrophin 1 (CT-1) as a central mediator of physiologic hypertrophy. We demonstrate that primary cardiomyocytes treated with recombinant human CT-1 protein engage a physiologic growth response, adding sarcomeres in series, a cellular/molecular change that is fully reversible with the removal of CT-1. This physiologic hypertrophy response to CT-1 is dominant, as CT-1 administration overrides the pathologic hypertrophy associated with agonists such as phenylephrine. In vivo delivery of human CT-1 protein leads to a rapid (14 days) alteration in the structure of the rat heart, with volume and wall dimension increases characteristic of exercise adaptation, changes that are fully reversible upon cessation of CT-1 treatment. In addition, CT-1 administration mitigates right heart failure in a model of pulmonary arterial hypertension, and sustains cardiac function in the post infarct rat heart. Finally, gene expression analysis revealed that CT-1 treatment leads to up-regulation of angiogenic factors within cardiomyocytes, suggesting that this cytokine engages a paracrine signaling mechanism to ensure that myocardial growth is matched by a robust angiogenesis.
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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 | 0.000 |
| 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 | 0.000 |
| 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".