Abstract 258: Angiotensin 1-7 Attenuates Endothelin-1-Induced Endothelial Cell Inflammation and Growth Through Nitric Oxide Production and Activation of Mas and EndothelinB Receptors
Bibliographic record
Abstract
In pulmonary hypertension, where the endothelin system plays a major role, the vasoprotective axis of the rennin angiotensin system (ACE2-Ang (1-7)-Mas) seems to be protective. However, the exact mechanisms are still elusive and whether Ang 1-7 counterbalancing effects are beyond interactions with Ang II system is unknown. In this study, we assessed whether Ang 1-7 influences/interacts with the ET-1 system in endothelial cells. Cultured human microvascular endothelial cells (HMEC) were studied. HMEC were stimulated with ET-1 (10-7 mol/L) in the absence and presence of Ang 1-7 (10-7 mol/L), BQ788 (an ETBR antagonist), BQ 123 (an ETAR antagonist) and A779 (Mas receptor inhibitor) (10-6 mol/L). Expression of pro-inflammatory mediator (VCAM-1), cell growth marker (PCNA), Mas, ETBR expression and eNOS activation was determined by immunoblotting. ET-1 significantly increased expression of VCAM-1 (138.90% vs control, p<0.05) and PCNA (125% vs control, p<0.05). Ang 1-7 alone did not modulate pro-inflammatory and growth mediators, but significantly inhibited the effects of ET-1 on VCAM-1 (95.55%) and PCNA (103.83%) expression, an effect mediated by Mas receptor activation (after A779: VCAM-1: 226.15%; PCNA: 120% vs control, p<0.05). Ang 1-7 increased NO production (Ctl: 7.5 vs Ang 1-7: 20 RFU/ug of protein, by microfluorescence). Inhibition of Ang 1-7-induced NO production by L-NAME, inhibited Ang 1-7-mediated effects on ET-1-induced VCAM-1 (160%) and PCNA (125%), p<0.05. Ang 1-7 significantly increased expression of ETB receptors (175.63% vs control, p<0.05), an effect attenuated by A779. Ang 1-7 (166.94% vs control, p<0.05) and ET-1 (146.04% vs control, p<0.05) increased eNOS phosphorylation in HMEC. Blockade of Mas and ETB receptor inhibited Ang 1-7 and ET-1 effects on eNOS activation. BQ123, but not BQ788, blocked ET-1-stimulated inflammation/growth in HMEC (VCAM-1: 75%, PCNA: 100%, p<0.05). In conclusion, Ang 1-7 negatively modulates proinflammatory and mitogenic actions of ET-1, through crosstalk between Mas and ETB receptors, and increase in NO production. These data highlight some molecular mechanisms whereby Ang 1-7 may exert beneficial effects in pulmonary hypertension and suggests a novel mechanism for Ang 1-7 signalling in HMEC.
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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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".