Interaction of Estrogen and Tumor Necrosis Factor α in Endothelial Cell Migration and Early Stage of Angiogenesis
Bibliographic record
Abstract
The role of estrogen replacement therapy in postmenopausal women remains controversial. The authors hypothesized that contradictory results with estrogen therapy may be explained by estrogen's potent proangiogenic property, which could be protective in women without atherosclerotic disease but in the presence of chronic inflammation, could lead to destabilization of atherosclerotic plaques. The authors thus examined the interaction between 17beta-estradiol (E2) and the inflammatory cytokine tumor necrosis factor alpha (TNFalpha) in an early stage of angiogenesis. Human umbilical endothelial cells were grown to confluence. Migration was assessed with a wound assay and proliferation was assessed with 5-bromo-2'-deoxyuridine (BrDU). Cells were treated with medium alone, TNFalpha at 0.3, 1, or 20 ng/ml, E2 at 20 nM, or the combination of E2 and TNFalpha. The authors used real-time polymerase chain reaction (PCR) to measure changes in expression of the angiogenesis genes angiopoeitin-2 (Ang-2), vacular endothelial growth factor (VEGF)-A and -C, and interleukin (IL)-8. A large dose of TNFalpha (20 ng/ml) inhibited healing at 24 to 48 h and the addition of E2 preserved some healing. E2 by itself doubled migration, with only a minimal effect on proliferation. A low dose of TNFalpha (0.3 ng/ml) had no effect on migration, 1.0 ng/ml moderately increased it, but the addition of E2 to both doses of TNFalpha increased migration. There was no change in migration when cells were pretreated with E2 and given TNFalpha after wounding, whereas pretreatment with TNFalpha followed by E2 significantly increased wound healing. The nitric oxide synthase (NOS) inhibitor N-nitro-l-arginine-methyl ester (l-NAME) completely blocked the E2 effect on migration. TNFalpha (0.3 and 1.0 ng/ml) increased expression of VEGF-C (2.8 +/- 0.1- and 2.5 +/- 0.2-fold, respectively) and IL-8 (32.8 +/- 1.2- and 42.7 +/- 3.6-fold, respectively) mRNA, but E2 had no significant effect on these molecules. E2 increases the angiogenic activity of TNFalpha. This could potentially worsen the stability of complex atherosclerotic plaques and increase cardiovascular events.
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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 | 0.001 | 0.001 |
| 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".