Regulation of the sarcoplasmic reticulum Ca<sup>2+</sup>-ATPase expression in the hypertrophic and failing heartThis paper is part of a series in the Journal's “Made in Canada” section. The paper has undergone peer review.
Bibliographic record
Abstract
The sarcoplasmic reticulum (SR) plays a central role in the contraction and relaxation coupling in the myocardium. The SR Ca(2+)-ATPase (SERCA2) transports Ca(2+) inside the SR lumen during relaxation of the cardiac myocyte. It is well known that diminished contractility of the hypertrophic cardiac myocyte is the main factor of ventricular dysfunction in the failing heart. A key feature of the failing heart is a decreased content and activity of SERCA2, which is the cause of some of the physiological defects observed in the hypertrophic cardiomyocyte performance that are important during transition of compensated hypertrophy to heart failure. In this review different possible mechanisms responsible for decreased transcriptional regulation of the SERCA2 gene are examined, which appear to be the primary cause for decreased SERCA2 expression in heart failure. The experimental evidence suggests that several signalling pathways are involved in the downregulation of SERCA2 expression in the hypertrophic and failing cardiomyocyte. Therapeutic upregulation of SERCA2 expression using replication deficient adenoviral expression vectors, pharmacological interventions using thyroid hormone analogues, beta-adrenergic receptor antagonists, and novel metabolically active compounds are currently under investigation for the treatment of uncompensated cardiac hypertrophy and heart failure.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.003 |
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".