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Sacubitril/valsartan mitigated intermittent hypoxia related intestinal microbiota alteration and aortic injury

  • Sleep Breathing Physiology and Disorders • Original Article
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Abstract

Objective

To investigate the influence of sacubitril valsartan sodium (SVS) on chronic intermittent hypoxia (IH) related gut microbiome composition alteration and aortic injury.

Methods

Experiments were performed using SD rats, which were divided into three groups: control, IH, and SVS group. O2 concentration was decreased to 7–8% at nadir approximately every 3 min in IH group (8 h per day for 6 weeks) or was left unchanged in control group. Rats in SVS group were orally gavaged with SVS at the dosage of 30 mg/kg/day (2 weeks after chronic IH exposure). At week 6, fecal and aortic samples were harvested for 16 s rDNA analysis and histological analysis, respectively.

Results

Principal coordinate analysis and non-metric multidimensional scaling analysis indicated that the bacterial community was altered by chronic IH exposure, while SVS treatment restored the intestinal microbial communities. Further analysis showed that IH decreased the relative abundance of Lactobacillus and Prevotella, while rats treated with SVS was enriched with Firmicutes, Bacilli, Prevotellaceae, and Lactobacillus, which was similar to control rats. Immunohistochemical staining showed that SVS prevented the upregulation of transforming growth factor-β1 and tumor necrosis factor-alpha in the aorta.

Conclusion

SVS prevented aortic adverse response to IH, possibly through modulating intestinal microbiota.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

The National Natural Science Foundation of China provided financial support in the form of National Natural Science funding (81800445). The sponsor had no role in the design or conduct of this research.

Author information

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000, Anhui Province, China

    Jinfeng Wang

  2. Department of Cardiology, The Second Affiliated Hospital of Wannan Medical College, 10# Kangfu Road, Wuhu, 241000, Anhui Province, China

    Hongxiang Zhang & Dasheng Lu

  3. Vascular Diseases Research Center of Wannan Medical College, Wuhu, China

    Hongxiang Zhang

  4. Department of Otolaryngology-Head and Neck Surgery, Yijishan Hospital of Wannan Medical College, Wuhu, China

    LiJuan Wu

  5. Translational Medicine Center of the Second Hospital Affiliated Wannan Medical College & Pathogens Detection Engineering Center of Wuhu, Wuhu, China

    Dasheng Lu

Authors
  1. Jinfeng Wang
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  4. Dasheng Lu
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Contributions

Animal experiment: Dasheng Lu and Jinfeng Wang; data analysis: Hongxiang Zhang and LiJuan Wu; project administration: Dasheng Lu; supervision: Dasheng Lu; writing: Dasheng Lu and Jinfeng Wang.

Corresponding authors

Correspondence to LiJuan Wu or Dasheng Lu.

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Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of Wannan Medical College. This article does not contain any studies with human participants performed by any of the authors.

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The authors declare no competing interests.

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Wang, J., Zhang, H., Wu, L. et al. Sacubitril/valsartan mitigated intermittent hypoxia related intestinal microbiota alteration and aortic injury. Sleep Breath 27, 1769–1777 (2023). https://doi.org/10.1007/s11325-023-02781-9

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  • DOI: https://doi.org/10.1007/s11325-023-02781-9

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