Abstract 13: P2X7 Receptor Knockout Attenuates Angiotensin II-Induced Hypertension, Vascular Injury And CD8 <sup>+</sup> T Cell Infiltration
Bibliographic record
Abstract
Background: The P2X7 receptor (P2RX7) recognizes damage associated molecule patterns such as adenosine triphosphate (ATP), and triggers the activation of immune cells. Elevated plasma ATP levels have been observed in hypertensive patients, providing a potential mechanism for P2RX7 activation. Additionally, a hypomorphic polymorphism for P2X7 is correlated with a decreased risk for essential hypertension in Chinese post-menopausal women. However, it is unknown whether P2RX7 activation contributes to angiotensin (Ang) II-induced blood pressure (BP) elevation and vascular damage. We hypothesized that P2rx7 knockout would blunt Ang II-induced BP elevation, vascular injury, and infiltration of activated immune T cells into perivascular adipose tissue (PVAT). Methods: Ten-to-12-week-old male C57BL/6J male wild-type (WT) and P2rx7 -/- mice were infused or not with Ang II (1000ng/kg/min) for 14 days. BP was determined by telemetry, mesenteric artery function and remodeling using pressurized myography, aortic stiffening by ultrasound and infiltration of activated immune T cells in aortic PVAT by flow cytometry. Results: Ang II-infused P2rx7 -/- mice display a reduced systolic BP (164±3 vs. 176±2 mm Hg, P <0.05) and pulse pressure (37±4 vs. 53±3 mm Hg, P <0.001) in comparison to WT mice. Aortic stiffening occurred in WT mice treated with Ang II, demonstrated by an increased pulse wave velocity (7.7±0.7 vs. 5.9±0.3 m/s, P <0.05), accompanied by a 3.8-fold increased infiltration of activated CD8 + T cells in aortic PVAT (60±16 vs 16±3 cells/aortic PVAT, P <0.001), which were both absent in P2rx7 -/- mice (6.4±1.4 vs 5.5±1.1 m/s and 27±7 vs 16±3 cells/aortic PVAT). In addition, the frequency of IFN-γ producing CD8 + T cells in the spleen of Ang II-treated WT mice increased (2.6±0.2% vs 1.2±0.2%), which did not occur in P2rx7 -/- mice (1.7±0.3% vs 1.7±0.2%). Ang II-infusion induced mesenteric artery endothelial dysfunction in WT mice (61±7 vs 83±4% relaxation response to acetylcholine, P <0.05), which was absent in P2rx7 -/- mice (89±3 vs 90±3%). Conclusion: P2rx7 knockout attenuates Ang II-induced hypertension, vascular injury, and infiltration of activated CD8 + T cells into aortic PVAT.
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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 | 0.000 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.007 | 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".