Differential growth state‐dependent activation of p38MAPK by treatment of endothelial cells with docosahexaenoic acid (DHA)
Bibliographic record
Abstract
Introduction Endothelial cells line the luminal surface of blood vessels and play an essential role in regulating vascular function. Endothelial cells quiescence is a primary property of the healthy endothelium, whereas cell proliferation is feature of vessel repair and progression of atherosclerosis. Docosahexaenoic acid (DHA), an omega‐3 fatty acid present in fish oil, is thought to exert an array of beneficial effects on vascular health by modulating endothelial function. However, a comparison of the effects of DHA on growing and confluent endothelial cells, which represent repairing and healthy states, respectively, has never been reported. Objective To investigate the effects of DHA on viability and proliferation of subconfluent (growing) and confluent (quiescent) human endothelial cells (EA.hy926) in relation to p38 mitogen‐activated protein kinase (MAPK) activation. Methods EA.hy926 endothelial cells were seeded on Matrigel‐coated plates and grown up to 10 days. Cells were treated with DHA (1–150 μM) for 24 h when they were either subconfluent (4 d after seeding) or confluent (8 d after seeding). Viability and proliferation were assessed. Phosphorylation of p38MAPK and mitogen‐activated protein kinase kinase (MKK3/MKK6) was assessed after treating subconfluent and confluent cells with 125 μM DHA over 8 h. Results Maximum cell number and DNA synthesis rate were reached on day 8, and the cells subsequently became quiescent. DHA >125 μM reduced viability of both growing and confluent cells after 24 h, while 40 μM slowed proliferation of both subconfluent and confluent cells. In subconfluent cells, 125 μM DHA activated p38MAPK and MKK3/MKK6 (a known upstream kinase), producing peaks at both 10 min and 4 h. In contrast, phospho‐p38MAPK and phospho‐MKK3/MKK6 peaks were only observed at 10 min in confluent cells. Conclusions Our study is the first to show a dose‐dependent effect of DHA on both proliferating and confluent endothelial cells with regards to viability and proliferation, as well as a growth state‐dependent activation of p38MAPK. This is highly relevant to how blood vessels respond to a dietary constituent such as DHA in various disease states. Since activation of stress‐stimulated protein p38MAPK, which is closely linked to pathological vascular remodeling, was observed in different growth conditions of cells, further studies to delineate the physiological effects of DHA on p38MAPK signal transduction in endothelial cells are warranted.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".