Dual agonism of peripheral cannabinoid CB1/CB2 receptors suppresses cardiac myocyte hypertrophy (652.9)
Bibliographic record
Abstract
The development of endocannabinoid‐based therapies is hindered by psychoactive side effects mediated by central CB1 receptors. We determined the effect of CB‐13, a peripherally‐restricted agonist of CB1/CB2 receptors, on cardiac myocyte hypertrophy. Endothelin‐1 (ET‐1, 0.1 μM) induced hypertrophy of rat cardiac myocytes as measured by cell enlargement (122±4%), protein synthesis ([3H]‐leucine incorporation; 147±13%), and fetal gene expression (brain natriuretic peptide mRNA levels; 426±88%) (p<0.05 vs. controls). CB‐13 attenuated all hypertrophic indicators and activated two anti‐hypertrophic signals: AMP‐activated protein kinase (AMPK) and eNOS through phosphorylation at Thr172 and Ser1177, respectively. eNOS activation was ablated by shRNA knockdown of AMPK, and disruption of signaling through AMPK (knockdown) or eNOS (L‐NIO, 1 μM) blocked the anti‐growth effects of CB‐13. CB‐13 also improved mitochondrial function by trafficking through AMPK and PGC‐1α (a driver of mitochondrial biogenesis). ET‐1‐induced mitochondrial depolarization, as assessed by subcellular compartmentalization of the potential‐sensitive dye, JC‐1, was inhibited by CB‐13. In conclusion, dual agonism of peripheral CB1/CB2 receptors is protective in the context of cardiac myocyte hypertrophy and mitochondrial dysfunction vis‐à‐vis crosstalk between AMPK, eNOS and PGC‐1α.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".