Phenylephrine‐induced cardiomyocyte hypertrophy and calcification are regulated by CD73‐TNAP interaction and inhibited by adenosine receptor activation
Bibliographic record
Abstract
CD73 has 5′ exonucleotidase activity converting AMP to adenosine (Ado) and inorganic phosphate (Pi). Ado supresses the activity of intracellular Tissue Nonspecific Alkaline Phosphatase (TNAP) resulting in decreased conversion of pyrophosphate (PPi) to Pi thus inhibiting intracellular calcification via increased PPi formation. We studied potential interplay between these systems in cultured rat ventricular myocytes treated for 24 h with 10 μM of the hypertrophic agent phenylephrine (PE). PE produced myocyte hypertrophy which was associated with a time‐dependent reduction in protein levels of CD73 (P<0.05) concomitant with marked increases in TNAP levels (P<0.05). The upregulation of TNAP was supressed by the non‐specific Ado analogue 2 chloro‐Ado whereas the downregulation of CD73 was only partially reduced. Inhibition of CD73 with α,β‐methylene ADP significantly reduced myocyte‐derived Ado levels by >;50%, produced a direct hypertrophic effect and sensitized cardiomyocytes to the pro‐hypertrophic effects of PE. The TNAP inhibitor tetramisole also reduced the hypertrophy and completely abrogated PE‐induced cardiomyocyte calcification, effects mimicked by 2 chloro‐Ado. Our results show that CD73 downregulation coupled with TNAP upregulation contribute to cardiomyocyte hypertrophy and injury which can be attenuated by exogenous Ado. Supported by the Heart and Stroke Foundation of Ontario.
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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) | 0.000 | 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) | 0.001 | 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 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".