Abstract P316: ANGIOTENSIN II-INDUCED LEFT VENTRICLE HYPERTROPHY AND DYSFUNCTION WERE EXAGGERATED BY <i>P2RX7</i> KNOCKOUT BUT UNAFFECTED BY P2RX7 PHARMACOLOGIC BLOCKADE
Bibliographic record
Abstract
Introduction: We have demonstrated that the P2X7 receptor (P2RX7), which activates immune cells via binding of extracellular adenosine triphosphate, plays a role in hypertension and vascular injury. Angiotensin (Ang) II-induced hypertension, vascular injury and perivascular infiltration of activated CD8 + T cells were attenuated by P2rx7 knockout or P2RX7 pharmacologic blockade. However, whether P2RX7 is involved in Ang II-induced cardiac dysfunction and hypertrophy remains unknown. Hypothesis: We hypothesized that Ang II-induced left ventricular (LV) dysfunction and hypertrophy will be blunted equally by P2rx7 knockout and P2RX7 antagonism. Methods: 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 group of WT mice infused with Ang II 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, and hypertrophic markers in cardiac ventricles by reverse transcription-quantitative PCR (RT-qPCR). Results: Ang II-induced increase in LV mass/body weight (6.3±0.2 vs 4.2±0.2 mg/g, P <0.001) and decrease in fractional shortening in WT mice (32.5±3.1% vs 43.8±2.4%, P <0.05) were exaggerated in P2rx7 -/- mice (7.3±0.5 mg/g and 20.2±3.1%, P <0.05), but not in mice receiving AZ10606120 (6.2±0.4 mg/g and 28.9±3.3%). Ang II-induced atrial natriuretic peptide ( Nppa /ribosomal protein S16 [ Rps16 ], 6.8±2.3 vs 1±0.1, P <0.001) and α-skeletal actin 1 expression ( Acta1 / Rps16 , 6.3±1.3 vs 1±0.2, P <0.001) tended to be further increased in P2rx7 -/- mice ( Nppa / Rps16 : 13.5±2.4 and Acta1 / Rps16 : 11.9±2.4), but not in AZ10606120-treated mice ( Nppa / Rps16 : 5.5±0.7 and Acta1 / Rps16 : 5.6±0.8). 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 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 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.003 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".