Inhibition of Lectin-Like Oxidized Low-Density Lipoprotein-1 Receptor Protects Against Plasma-Mediated Vascular Dysfunction Associated With Pre-Eclampsia
Bibliographic record
Abstract
BACKGROUND: Pre-eclampsia (PE) is associated with vascular endothelial dysfunction and oxidative stress initiated by impaired trophoblast invasion. Oxidative stress modifies circulating low-density lipoprotein (LDL) to oxidized LDL (oxLDL). Lectin-like oxLDL receptor-1 (LOX-1) is a scavenger receptor for oxLDL. We hypothesized that plasma from patients with PE alters LOX-1 in normal human vessels during pregnancy, causing oxLDL-induced impairment of vascular function. METHODS: Control-matched plasma was obtained from women with PE (n = 6). Oxidized LDL and soluble LOX-1 levels were determined by enzyme-linked immunoassay (ELISA). Remaining plasma was pooled and stored at -80ºC. Human omental arteries were incubated in 3% plasma from normal pregnant (NP) women or plasma from women with PE. Expression of LOX-1 in these vessels was determined by immunohistochemistry with antibodies against LOX-1. The omental vessels were exposed to oxLDL and the LOX-1 inhibitor TS20. Vascular function was assessed in response to the vasoconstrictor U46619 and the vasodilators bradykinin (BK) and sodium nitroprusside (SNP). RESULTS: No significant differences in the concentrations of oxLDL or soluble LOX-1 (sLOX-1) were found in plasma from women with PE as compared with NP women. The expression of LOX-1 was not significantly different in either the NP or PE incubated omental vessels. Incubation of vessels from NP women in plasma from women with PE impaired their relaxation in response to BK as compared with that of NP vessels incubated in plasma from NP women. Exposure to oxLDL further impaired relaxation in NP vessels incubated with plasma from women with PE. Inhibition of LOX-1 protected against the impairment of vascular relaxation induced by plasma from women with PE. CONCLUSION: Inhibition of LOX-1 prevents endothelial dysfunction in an in vitro model of PE and may prove useful as a therapeutic target in the treatment of PE.
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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 | 0.001 | 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 | 0.000 | 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".