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Updated: Jun 30, 2025

Separation and Differential Characterization of Gut Microbial Extracellular Vesicles in Salt-Sensitive Rats under High-Salt Diet Conditions
Published on: June 6, 2025
Akkermansia muciniphila extracellular vesicles have a protective effect against hypertension
Jee Young Kim1,2,3,4, Cheong-Wun Kim1,2,3,4, Su Young Oh5
1Department of Pharmacology, Kyungpook National University, Daegu, 41944, Republic of Korea.
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.
Insights
Akkermansia muciniphila extracellular vesicles (AmEVs) show promise in treating hypertension by increasing T regulatory cells and reducing inflammation, without adverse effects. AmEVs may offer a novel therapeutic approach for hypertension management.
Area of Science:
- Microbiology
- Immunology
- Cardiovascular Science
Background:
- Akkermansansia muciniphila (Am) is recognized for its probiotic benefits in metabolic syndrome.
- The precise mechanisms underlying Am's therapeutic effects, particularly in hypertension, require further investigation.
Purpose of the Study:
- To investigate the protective effects of Am extracellular vesicles (AmEVs) against hypertension.
- To elucidate the underlying immunological mechanisms of AmEVs in hypertension.
Main Methods:
- AmEVs were purified and characterized using nanoparticle tracking analysis, transmission electron microscopy, and SDS-PAGE.
- Organ bath studies assessed AmEVs' effects on vascular contraction and relaxation.
- In vivo studies involved weekly tail vein injections of AmEVs into Wistar-Kyoto rats and spontaneously hypertensive rats over 4 weeks.
- Immunological analyses included flow cytometry, RT-qPCR, and Western blot on PBMCs and splenocytes.
Main Results:
- AmEVs did not directly affect vascular contraction or endothelial relaxation in thoracic aortas.
- AmEVs demonstrated a protective effect against hypertension development in spontaneously hypertensive rats.
- Treatment with AmEVs led to an increased population of T regulatory cells and a trend towards reduced proinflammatory cytokines.
- No serious adverse reactions were observed in the AmEVs-treated rats.
Conclusions:
- Am extracellular vesicles possess a protective effect against hypertension.
- AmEVs modulate immune responses by increasing T regulatory cells and decreasing proinflammatory cytokines.
- AmEVs represent a potential novel therapeutic strategy for hypertension treatment.
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