Microvascular Endothelial Dysfunction in Obesity Is Driven by Macrophage-Dependent Hydrogen Sulfide Depletion
Why this work is in the frame
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Bibliographic record
Abstract
Objective— The function of perivascular adipose tissue as an anticontractile mediator in the microvasculature is lost during obesity. Obesity results in inflammation and recruitment of proinflammatory macrophages to the perivascular adipose tissue that is paralleled by depletion of the vasorelaxant signaling molecule hydrogen sulfide (H 2 S) in the vessel. The current objective was to assess the role of macrophages in determining vascular [H 2 S] and defining how this impinged on vasodilation. Approach and Results— Contractility and [H 2 S] were measured in mesenteric resistance arterioles from lean and obese mice by using pressure myography and confocal microscopy, respectively. Vasodilation was impaired and smooth muscle and endothelial [H 2 S] decreased in vessels from obese mice compared with those from lean controls. Coculturing vessels from lean mice with macrophages from obese mice, or macrophage-conditioned media, recapitulated obese phenotypes in vessels. These effects were mediated by low molecular weight species and dependent on macrophage inducible nitric oxide synthase activity. Conclusions— The inducible nitric oxide synthase activity of perivascular adipose tissue–resident proinflammatory macrophages promotes microvascular endothelial dysfunction by reducing the bioavailability of H 2 S in the vessel. These findings support a model in which vascular H 2 S depletion underpins the loss of perivascular adipose tissue anticontractile function in obesity.
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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 | 0.000 | 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 | 0.000 |
| 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 it