Apoptosis of endothelial cells leads to paracrine induction of Bcl-xl in vascular smooth muscle cells
Bibliographic record
Abstract
Disregulation of the apoptotic process in the vessel wall plays an important role in initiation and progression of atherosclerosis. Resistance to apoptosis in vascular smooth muscle cells (VSMC) has been implicated in the development of myo-intimal thickening associated with atherosclerosis. In the present study we evaluated the potential role of apoptosis of EC in generating a microenvironment favoring resistance to apoptosis in VSMC. Apoptosis was induced in human umbilical vein endothelial cells (HUVEC) by serum starvation (SS). The extent of cell death was quantitated with crystal violet viability assays and apoptosis was confirmed by morphological and fluorescence studies. Serum-free media conditioned by apoptotic EC were used to serum-starve vascular smooth muscle cells (VSMC). Conditioned medium was found to significantly enhance the survival of VSMC as compared to unconditioned serum-free media. This paracrine pro-survival activity was due to inhibition of apoptosis and not to a increased proliferation rate of surviving cells since (i) thymidine incorporation in VSMC was not increased by exposure to conditioned medium and (ii) the development of classical morphological apoptotic features was significantly inhibited in VSMC exposed to medium conditioned by apoptotic EC as compared to unconditioned serum-free media. Exposure of VSMC to conditioned medium was associated with increased expression of the anti-apoptotic protein Bcl-(x)l. Significant attenuation of the anti-apoptotic activity was found with IGF-1 blockade, suggesting that IGF-1 is a component of the anti-apoptotic paracrine loop activated during apoptosis of EC. These results suggest that apoptosis of EC leads to activation of a paracrine anti-apoptotic loop active on VSMC. Activation of this loop could represent an important initiating event favoring the development of myointimal thickening secondary to endothelial injury, a key feature of chronic vascular diseases.
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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 | 0.000 |
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".