Low-Density Lipoprotein Inhibits Receptor-Mediated Prostaglandin Synthesis without Affecting Calcium and Arachidonic Acid Mobilization in Human Endothelial Cells
Bibliographic record
Abstract
Vascular serotonin 5-HT1 receptors have quiescent constrictor activity that is activated by other vasoactive agents such as histamine. Previously, we observed that the 5-HT1-selective agonist 5-carboxamidotryptamine (5-CT) potentiated histamine-stimulated arachidonic acid (AA) mobilization and prostaglandin production in human aortic endothelial cells (HAEC). In the present study, 5-CT was found to potentiate histamine-stimulated calcium mobilization but had no effect on intracellular calcium when added alone. Treatment of HAEC with human low-density lipoprotein (LDL) for 20 hours inhibited the histamine- plus 5-CT-stimulated production of prostaglandin F2alpha (PGF2alpha) and the prostacyclin metabolite 6-keto-PGF1alpha. However, the effects of histamine and histamine potentiation by 5-CT on intracellular Ca mobilization and AA release were resistant to LDL treatment. Conversely, the subsequent receptor-independent conversion of AA to prostaglandins was inhibited by LDL. These results demonstrate that histamine and serotonin receptor activity, measured as the stimulation of Ca and AA mobilization, is resistant to LDL exposure under mild oxidizing conditions, whereas the receptor-independent synthesis of prostaglandins is inhibited by LDL. The results also suggest that the LDL-stimulated mobilization of cellular AA is responsible for the LDL-mediated inhibition of prostaglandin synthesis. These findings suggest a mechanism by which LDL and/or atherosclerosis could promote the vascular liberation of AA that is not converted to endothelium-derived prostaglandins and is therefore available as substrate for the production of other eicosanoids.
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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) | 0.002 | 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".