Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Adipose tissue–secreted extracellular vesicles (EVs) containing microRNAs (miRNAs) convey intercellular message signaling. The biogenesis of EV‐miRNAs from perivascular adipose tissue (PVAT) and their roles in intercellular communication in response to obesity‐associated inflammation have not yet been fully explored. By feeding mice a high‐fat diet for 16 wk, we established obesity‐associated, chronic low‐grade inflammation in PVAT, characterized as hypertrophy of perivascular adipocytes, decreased adipogenesis, and proinflammatory macrophage infiltration. We show that PVAT‐derived EVs and their encapsulated miRNAs can be taken up into vascular smooth muscle cells (VSMCs) in vivo and in vitro . miR‐221‐3p is one of the highly enriched miRNAs in obese PVAT and PVAT‐derived EVs. Transfer and direct overexpression of miR‐221‐3p dramatically enhances VSMC proliferation and migration. Peroxisome proliferator–activated receptor γ coactivator 1α is identified as a miR‐221‐3p target in VSMC phenotypic modulation. Obese mice secrete abundant miRNA‐containing EVs, evoking inflammatory responses in PVAT and vascular phenotypic switching in abdominal aorta of lean mice. Local delivery of miR‐221‐3p mimic in femoral artery causes vascular dysfunction by suppressing the contractile genes in the arterial wall. Our findings provide an EV–miR‐221‐3p–mediated mechanism by which PVAT triggers an early‐stage vascular remodeling in the context of obesity‐associated inflammation.—Li, X., Ballantyne, L. L., Yu, Y., Funk, C. D. Perivascular adipose tissue–derived extracellular vesicle miR‐221‐3p mediates vascular remodeling. FASEB J. 33, 12704–12722 (2019). www.fasebj.org
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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 | 0.001 |
| 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) | 0.001 | 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 it