Faculty Opinions recommendation of Early rescue of lymphatic function limits atherosclerosis progression in Ldlr-/- mice.
Bibliographic record
Abstract
BACKGROUND AND AIMS: Our previous data showed that lymphatic function impairment occurs before the onset of atherosclerosis in mice and is precociously associated with a defect in the propelling capacity of the collecting lymphatic vessels. Concomitantly, we found that lymphatic transport can be restored in mice by systemic injections of a mutant form of VEGF-C (VEGF-C 152s), a growth factor known to increase mesenteric collecting lymphatic vessel pumping through a VEGFR-3-dependent mechanism in rats. In the present study, we aimed to determine whether and how early modulation of collecting lymphatic vessel function could restrain atherosclerosis onset and limit its progression.METHODS: Before the administration of a pro-atherosclerotic regimen, Ldlr-/- mice at 6 weeks of age were injected intraperitoneally with VEGF-C 152s or PBS every other day for 4 weeks, fed on high fat diet (HFD) for an additional 8 weeks to promote plaque progression, and switched back on chow diet for 4 more weeks to stabilize the lesion.RESULTS: Early treatment with VEGF-C first improved lymphatic molecular transport in 6-week-old Ldlr-/- mice and subsequently limited plaque formation and macrophage accumulation, while improving inflammatory cell migration through the lymphatics in HFD-fed mice. The contraction frequency of the collecting lymphatic vessels was significantly increased following treatment throughout the whole atherosclerotic process and resulted in enhanced plaque stabilization. This early and maintained rescue of the lymphatic dysfunction was associated with an upregulation of VEGFR3 and FOXC2 expression on lymphatic endothelial cells.CONCLUSIONS: These results suggest that early treatments that specifically target the lymphatic contraction capacity prior to lesion formation might be a novel therapeutic approach for the prevention and treatment of atherosclerosis.Copyright © 2019 Elsevier B.V. All rights reserved. PMID: 30851674 Funding information This work was supported by: CIHR, Canada
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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 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".