PS-BPB02-4: LEFT VENTRICLE HYPERTROPHY AND DYSFUNCTION WERE EXAGGERATED BY P2RX7 KNOCKOUT BUT UNAFFECTED BY P2RX7 PHARMACOLOGIC BLOCKADE IN ANGIOTENSIN II-INFUSED MICE
Bibliographic record
Abstract
Objective: Extracellular adenosine triphosphate released from damaged cells binds to the P2X7 receptor (P2RX7) to activate of immune cells. Our preliminary data demonstrated that P2RX7 plays a role in vascular injury of hypertensive mice. Angiotensin (Ang) II-induced hypertension, vascular injury and aortic perivascular infiltration of activated T cell were attenuated by P2rx7 knockout or P2RX7 pharmacologic blockade. However, whether P2RX7 is involved in Ang II-induced cardiac dysfunction and hypertrophy is unknown. We hypothesized that Ang II-induced left ventricular (LV) dysfunction and hypertrophy would be blunted by P2rx7 knockout or P2RX7 antagonism. Design and method: Ten-to-12-week-old male C57BL/6J wild-type (WT) and P2rx7-/- mice were infused or not with Ang II (1000 ng/kg/min) for 14 days. A second set of Ang II-infused WT mice was infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle for 14 days. Cardiac LV function and remodeling were determined by ultrasound. Total RNA was isolated from the heart using the mirVana miRNA isolation kit. Relative expression was calculated using the Pfaffl method with 40S ribosomal protein S16 ( Rps16 ) as a reference gene. Hypertrophic and fibrotic markers were studied by reverse transcription-quantitative PCR (RT-qPCR) in cardiac ventricles. Results: Ang II-induced 1.5-fold increase in LV mass/body weight ( P < 0.001) and ∽25% decrease in fractional shortening in WT mice and mice receiving AZ10606120 (P < 0.05). These changes were exaggerated in P2rx7-/- mice (LV mass/body weight: 1.7-fold increase, fractional shortening: 54% decrease, P < 0.05), but not in mice receiving AZ10606120. Ang II-induced atrial natriuretic peptide ( Nppa/Rps16 : 7-fold, P < 0.001) and α-skeletal actin 1 expression ( Acta1/Rps16 : 6-fold, P < 0.001) tended to be further increased in P2rx7-/- mice ( Nppa/Rps16 : 14-fold and Acta1/Rps16 : 12-fold), but not in AZ10606120-treated mice. Ang II-induced myosin heavy chain 7B (14-fold, P < 0.05) was unaffected by P2rx7 knockout or P2RX7 antagonism. Ang II caused a 1.5-fold increase in transforming growth factor β; 1 only in P2rx7-/- mice ( P < 0.05). Conclusion: Ang II-induced LV hypertrophy and dysfunction were exaggerated by P2rx7 knockout but were not affected by P2RX7 pharmacologic blockade.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".