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Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension

Hypertension Research (2024)Cite this article

Abstract

Akkermansia muciniphila (Am) shows a beneficial role as a probiotic in the treatment of metabolic syndrome. However, the mechanism remains to be elucidated. We tested the hypothesis that Am extracellular vesicles (AmEVs) have a protective effect against hypertension. Extracellular vesicles purified from anaerobically cultured Am were characterized by nanoparticle tracking analysis, transmission electron microscopy, and silver stain after sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). AmEVs (1.0 × 1010 log particles/L) or vehicles were added into organ baths to induce vasorelaxation. In addition, AmEVs (1.0 × 108 or 1.0 × 109 particles/kg) or vehicles were injected into the tail veins of Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) weekly for 4 weeks. Peripheral blood mononuclear cells (PBMCs) and splenocytes isolated from both rat strains were analyzed by flow cytometry, RT-qPCR, and western blot. AmEVs affected neither vascular contraction nor endothelial relaxation in thoracic aortas. Moreover, AmEVs protected against the development of hypertension in SHRs without a serious adverse reaction. Additionally, AmEVs increased the population of T regulatory (Treg) cells and tended to reduce proinflammatory cytokines. These results indicate that AmEVs have a protective effect against hypertension without a serious adverse reaction. Therefore, it is foreseen that AmEVs may be utilized as a novel therapeutic for the treatment of hypertension.

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Acknowledgements

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (NRF-2021R1A2B502001763, and 2021R1A4A1021617), and a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI15C0001).

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Author notes

  1. These authors contributed equally: Jee Young Kim, Cheong-Wun Kim

Authors and Affiliations

  1. Department of Pharmacology, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Cheong-Wun Kim, Sungmin Jang, Olarinoye Zainab Yetunde & Inkyeom Kim

  2. Cardiovascular Research Institute, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Cheong-Wun Kim, Sungmin Jang, Olarinoye Zainab Yetunde, Bo A Kim & Inkyeom Kim

  3. BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Cheong-Wun Kim, Sungmin Jang, Olarinoye Zainab Yetunde & Inkyeom Kim

  4. Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea

    Jee Young Kim, Cheong-Wun Kim, Sungmin Jang, Olarinoye Zainab Yetunde & Inkyeom Kim

  5. Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, 41944, Republic of Korea

    Su Young Oh & Su-Hyung Hong

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Kim, J.Y., Kim, CW., Oh, S.Y. et al. Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01627-5

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