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Coenzyme Q10 inhibits intracranial aneurysm formation and progression in a mouse model

Abstract

Background

The aim of this study was to investigate the effect of coenzyme Q10 (CoQ10), a commonly used nutritional supplement, on intracranial aneurysm (IA) initiation and progression in a mouse model, as well as the mechanism.

Methods

Hydrogen peroxide (H2O2) was used to treat mouse-derived vascular smooth muscle cells (VSMCs) to induce oxidative injury, followed by incubation with CoQ10. In the mouse IA model established by elastase injection, CoQ10 was orally administered at 10 mg/kg every other day for 14 days, during which the incidence of IA, rupture rate, symptom-free survival, and systolic blood pressure were recorded.

Results

CoQ10 promoted the expression of nuclear factor erythroid 2-related factor 2 and antioxidant enzymes. In H2O2-treated VSMCs, reactive oxygen species and cell apoptosis were reduced by CoQ10. In IA mice, CoQ10 treatment decreased the rupture rate of IA, improved the symptom-free survival, and reduced systolic blood pressure. Macrophage infiltration and expression of pro-inflammatory cytokines in the cerebral arteries were mitigated by CoQ10 treatment.

Conclusions

CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice. CoQ10 also alleviates inflammation and restores normal phenotypes of VSMCs in the cerebral arteries. Our data suggest that CoQ10 is a potentially effective drug for managing IA.

Impact

  • To investigate the effect of CoQ10, a commonly used nutritional supplement, on IA initiation and progression in a mouse model, as well as the mechanism.

  • CoQ10 promoted the expression of Nrf2 and antioxidant enzymes. In H2O2-treated VSMCs, ROS and cell apoptosis were reduced by CoQ10.

  • CoQ10 is effective in reducing oxidative stress in VSMCs, thereby attenuating IA formation and rupture in mice.

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Fig. 1: CoQ10 treatment activated Nrf2 signaling in H2O2-incubated VSMCs.
Fig. 2: Effect of CoQ10 on the production of reactive oxygen species (ROS) and cell viability of H2O2-incubated VSMCs.
Fig. 3: CoQ10 administration prevents the formation and rupture of intracranial aneurysms (IAs) in a mouse model.
Fig. 4: CoQ10 administration inhibited macrophage infiltration and reduced expression of pro-inflammatory cytokines.
Fig. 5: CoQ10 administration modulates the phenotype of VSMC in vivo.

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Acknowledgements

This study was supported by Science and Technology Project of Quanzhou City of Fujian Province (2018T007R).

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Data collection and analysis: J.H., H.Z., L.Y., J.Z., and Z.J.; study designed and manuscript writing: J.H. and J.Z. All authors approved the final submission.

Corresponding author

Correspondence to Zhixian Jiang.

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The authors declare no competing interests.

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Huang, J., Zhang, H., You, L. et al. Coenzyme Q10 inhibits intracranial aneurysm formation and progression in a mouse model. Pediatr Res (2021). https://doi.org/10.1038/s41390-021-01512-8

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