Abstract 118: P2X7 Receptor Contributes To Angiotensin II-induced Hypertension, Vascular Injury And Cd8 <sup>+</sup> T Cell Activation
Bibliographic record
Abstract
Introduction: Innate and adaptive immune cells contribute to hypertension and end-organ damage. High blood pressure (BP) causes cardiovascular injury and the release of damage-associated molecule patterns such as adenosine triphosphate (ATP). ATP can bind to the purinergic receptor P2X7 (P2RX7) on innate immune cells triggering interleukin-1β release, which drives further immune activation. Hypothesis: We hypothesized that P2rx7 knockout or P2RX7 antagonism would blunt angiotensin II (AngII)-induced BP elevation and cardiovascular injury through decreased immune activation. Methods: Ten-to-12-week-old male C57BL/6J wild-type (WT) and P2rx7 -/- mice were infused or not with AngII (1000 ng/kg/min) for 14 days. A second group of AngII-infused WT mice was also infused with the P2RX7 antagonist AZ10606120 (694 ng/kg/min) or vehicle. BP was determined by telemetry, plasma ATP using a bioluminescence assay, mesenteric artery function using pressurized myography, cardiac left ventricle (LV) function and mass by ultrasound and activated immune T cell infiltration in aortic perivascular adipose tissue (PVAT) by flow cytometry. Results: AngII increased plasma ATP in WT mice (4.4±1.2 vs 2.0±0.9 μM, P <0.05). AngII-induced systolic BP elevation was reduced by P2rx7 deficiency (164±3 vs 176±2 mm Hg, P <0.05) or P2RX7 antagonism (143±5 vs 170±5 mm Hg, P <0.01). AngII decreased LV fractional shortening (FS, 32.5±3.1% vs 43.8±2.4%, P <0.05) and increased LV mass/body weight (BW) in WT mice (LVmass/BW, 6.3±0.2 vs 4.2±0.2 mg/g, P <0.001), which were exaggerated in P2rx7 -/- (FS: 20.2±3.1% and LVmass/BW: 7.2±0.5 mg/g, P <0.05), but not in mice receiving AZ10606120. AngII reduced the dilatation response of mesenteric arteries to acetylcholine in WT (61±7 vs 83±4%, P <0.05), but not in P2rx7 -/- or AZ10606120-treated mice. AngII increased CD69 + CD8 + T cell infiltration in aortic PVAT of WT (60±16 vs 16±3 cells/aortic PVAT, P <0.001), but not in P2rx7 -/- or AZ10606120-treated mice. Conclusion: P2rx7 knockout or antagonism attenuates AngII-induced BP elevation, vascular injury, and infiltration of activated CD8 + T cells into aortic PVAT. P2rx7 knockout exacerbated AngII-induced cardiac dysfunction and hypertrophy, whereas P2RX7 antagonism did not.
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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 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.011 | 0.004 |
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".