# Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice.
> 水素分子はLDL受容体ノックアウトマウスにおけるアテローム性動脈硬化プラークを安定化する


## Abstract

Using LDLR-knockout mice fed an atherogenic diet, daily H2 administration was evaluated alongside simvastatin for effects on plaque composition and stability. H2 increased collagen content within plaques while reducing macrophage infiltration, lipid accumulation, and dendritic cell numbers; regulatory T cell counts rose concurrently. Circulating oxidized-LDL levels and aortic reactive oxygen species were both diminished, and plaque apoptosis was reduced. Cell-based experiments using oxidized-LDL-stimulated macrophage-derived foam cells demonstrated that H2 suppressed endoplasmic reticulum stress responses comparably to the chemical inhibitor 4-phenylbutyric acid, and scavenged cellular ROS similarly to N-acetylcysteine. Nrf2 activation by H2 was confirmed, and silencing Nrf2 with siRNA abolished the cytoprotective effect, indicating that dual suppression of endoplasmic reticulum stress and activation of the Nrf2 antioxidant pathway underlie H2-mediated plaque stabilization.

### Mechanism

H2 suppresses endoplasmic reticulum stress signaling and activates the Nrf2 antioxidant pathway, thereby reducing apoptosis in macrophage-derived foam cells and improving atherosclerotic plaque stability. ROS scavenging in the aorta further contributes to the stabilizing effect.

## Bibliographic

- **Authors**: Song G, Zong C, Zhang Z, Yu Y, Yao S, Jiao P, et al.
- **Journal**: Free Radic Biol Med
- **Year**: 2015
- **PMID**: [26117323](https://pubmed.ncbi.nlm.nih.gov/26117323/)
- **DOI**: [10.1016/j.freeradbiomed.2015.06.018](https://doi.org/10.1016/j.freeradbiomed.2015.06.018)
- **Study type**: animal study
- **Delivery route**: mixed routes
- **Effect reported**: positive

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 26117323. https://h2-papers.org/en/papers/26117323
> **Source**: PubMed PMID [26117323](https://pubmed.ncbi.nlm.nih.gov/26117323/)