CSE‐Derived Hydrogen Sulfide Safeguards Vascular Iron Homeostasis by Coupling Ferritin Buffering to Vasoprotection
Bibliographic record
Abstract
ABSTRACT Iron overload drives oxidative stress and vascular injury, yet the role of hydrogen sulfide (H 2 S) in systemic and vascular iron regulation remains unclear. We investigated how cystathionine γ‐lyase (CSE)‐derived H 2 S influences iron handling and vascular responses following acute iron overload. Wild‐type (WT) and CSE‐knockout (CSE‐KO) mice received PBS, low‐concentration (1×) or high‐concentration (3×) iron dextran intravenously. CSE‐KO mice exhibited elevated serum iron and transferrin saturation but impaired ferritin upregulation compared to WT. KO aortas showed greater iron deposition, elastin degradation, and inflammatory remodeling under high iron. Iron overload impaired phenylephrine‐induced vasocontraction and H 2 S‐mediated vasorelaxation, with CSE‐KO mice displaying the most severe vascular dysfunction and elevated blood pressure. WT mice compensated via CSE upregulation and increased H 2 S production. Our findings demonstrate that CSE/H 2 S deficiency disrupts ferritin‐mediated iron storage, exacerbates vascular iron accumulation, and worsens vasomotor dysfunction during iron overload. The CSE/H 2 S pathway may represent a therapeutic target for mitigating iron‐induced vascular damage.
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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) | 0.001 | 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".