Angiotensin II-induced MMP-2 release from endothelial cells is mediated by TNF-α
Bibliographic record
Abstract
Angiotensin II (ANG II) has been etiologically linked to vascular disease; however, its role in the alterations of endothelial function that occur in vascular disorders is not completely understood. Matrix metalloproteinases (MMPs) and proinflammatory cytokines are involved in the pathological remodeling of blood vessels that occurs in vascular disease. In this study we evaluated the effects of ANG II on tumor necrosis factor (TNF)-alpha and MMP-2 production in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were stimulated with ANG II (0.1-10 microM) for 24 h, in the presence or absence of antagonists of ANG II type 1 (AT(1)R) and type 2 (AT(2)R) receptors, and the production and release of TNF-alpha and MMP-2 were assessed. ANG II increased TNF-alpha mRNA and protein expression and the release of bioactive TNF-alpha. Moreover, ANG II induced MMP-2 release and reduced the secretion of tissue inhibitor of MMP (TIMP)-2 from endothelial cells. To elucidate whether endogenous TNF-alpha could mediate the effects of ANG II on MMP-2 release, cells were pretreated with anti-TNF-alpha neutralizing antibodies or pentoxifylline (an inhibitor of TNF-alpha synthesis). TNF-alpha inhibition prevented the secretion of MMP-2 induced by ANG II. Furthermore, AT(1)R antagonism with candesartan prevented the formation of MMP-2 and TNF-alpha and the reduction of TIMP-2 induced by ANG II. These results indicate that ANG II, via AT(1)R, modulates the secretion of TNF-alpha and MMP-2 from endothelial cells and that TNF-alpha mediates the effects of ANG II on MMP-2 release.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".