Pld-dependent generation of oxygen species is increased in ang ii-stimulated vascular smooth muscle cells from hypertensive patients
Bibliographic record
Abstract
We tested the hypothesis that augmented Ang II-induced vascular smooth muscle cell (VSMC) growth in human hypertension is mediated via PLD-dependent pathways that generate reactive oxygen species (ROS). VSMCs from arteries of normotensive and hypertensive subjects were studied. Production of ROS was measured with dichlorofluorescin diacetate, (8 μM). The roles of PLD and NADH/NADPH oxidase were assessed with the specific inhibitors, dihydro-D-erythro-sphingosine (10 μM) and diphenylene iodinium (DPI) (10 μM) respectively. PLD activity was measured by the transphosphatidylation assay. Ang II increased fluorescence. This effect was inhibited by catalase, indicating that the fluorescence signal was derived predominantly from H2O2. Ang II increased H2O2 production within 1 hour. Responses were greater (p < 0.05) in cells from hypertensive patients (Emax = 79 ± 8 nM) than normotensive subjects (Emax = 65 ± 3 nM). DPI inhibited (p < 0.01) Ang II-stimulated H2O2 responses, as well as Ang II-induced DNA synthesis, as measured by 3H-thymidine incorporation. PLD inhibition attenuated (p < 0.05) Ang II effects on H2O2 production in cells from hypertensive (Emax = 42 ± 8 nM) and normotensive subjects (Emax = 33 ± 11 nM). Ang II-stimulated PLD activity was greater (p < 0.01) in cells from hypertensive (202 ± 39% of control) compared with normotensive subjects (151 ± 18% of control). In VSMCs from hypertensive patients, Ang II-induced generation of ROS is augmented. These effects are mediated via PLD-dependent, NADH/NADPH oxidase-sensitive pathways. Thus increased PLD activity is associated with increased oxidative stress that may underlie enhanced VSMC growth in human hypertension.
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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) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".