Gut Microbiota Promote Angiotensin II–Induced Arterial Hypertension and Vascular Dysfunction
Open accessAbstract
Background: The gut microbiome is essential for physiological host responses and development of immune functions. The impact of gut microbiota on blood pressure and systemic vascular function, processes that are determined by immune cell function, is unknown. Methods and Results: Unchallenged germ‐free mice ( GF ) had a dampened systemic T helper cell type 1 skewing compared to conventionally raised ( CONV ‐R) mice. Colonization of GF mice with regular gut microbiota induced lymphoid mRNA transcription of T‐box expression in T cells and resulted in mild endothelial dysfunction. Compared to CONV ‐R mice, angiotensin II (Ang II ; 1 mg/kg per day for 7 days) infused GF mice showed reduced reactive oxygen species formation in the vasculature, attenuated vascular mRNA expression of monocyte chemoattractant protein 1 ( MCP ‐1), inducible nitric oxide synthase (iNOS) and NADPH oxidase subunit Nox2, as well as a reduced upregulation of retinoic‐acid receptor‐related orphan receptor gamma t (Rorγt), the signature transcription factor for interleukin (IL)‐17 synthesis. This resulted in an attenuated vascular leukocyte adhesion, less infiltration of Ly6G + neutrophils and Ly6C + monocytes into the aortic vessel wall, protection from kidney inflammation, as well as endothelial dysfunction and attenuation of blood pressure increase in response to Ang II . Importantly, cardiac inflammation, fibrosis and systolic dysfunction were attenuated in GF mice, indicating systemic protection from cardiovascular inflammatory stress induced by AngII. Conclusion: Gut microbiota facilitate Ang II ‐induced vascular dysfunction and hypertension, at least in part, by supporting an MCP ‐1/ IL ‐17 driven vascular immune cell infiltration and inflammation.
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The gut microbiota constantly communicates with vital organ systems of the host, such as the brain, bone marrow, vasculature, kidney, immune system and autonomic nervous system (ANS).
“The gut microbiota constantly communicates with vital organ systems of the host, such as the brain6, bone marrow7, vasculature8, kidney9, immune system10 and autonomic nervous system (ANS)11,12.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [8]
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- Authors
- Karbach, S. H., Schönfelder, T., Brandão, I., Wilms, E., Hörmann, N., Jäckel, S., Schüler, R., Finger, S., Knorr, M., Lagrange, J., Brandt, M., Waisman, A., Kossmann, S., Schäfer, K., Münzel, T., Reinhardt, C., & Wenzel, P.
- Affiliations
- Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- German Centre for Cardiovascular Research (DE)
- Corresponding author
- Wenzel, Philip
- ORCID
- Venue
- Journal of the American Heart Association
- Published
- 2016-09
- Volume
- 5
- Issue
- 9
- ISSN
- 2047-9980 (ISSN-L)
- PMC
- PMC5079031
- OpenAlex
- W2508585495
- Cited by
- 378
- References
- 46
- Citations by year
- 2026: 8 · 2025: 35 · 2024: 44 · 2023: 40 · 2022: 52 · 2021: 64 · 2020: 49 · 2019: 38 · 2018: 24 · 2017: 23 · 2016: 1
- FWCI
- 14.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of the American Heart Association (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- gut microbiota, angiotensin II, hypertension, vascular dysfunction, endothelial dysfunction, germ-free mice, T helper cell differentiation, T-bet, RORγt, IL-17, MCP-1, inducible nitric oxide synthase, NADPH oxidase NOX2, reactive oxygen species, monocyte infiltration, neutrophils, renal inflammation, cardiac inflammation, myocardial fibrosis, systolic dysfunction, vascular inflammation
- MeSH terms
- Gastrointestinal Microbiome, NADPH Oxidase 2, Angiotensin II, Animals, Aorta, Blood Vessels, Cell Adhesion, Endothelium, Vascular, Germ-Free Life, Hypertension, Leukocytes, Monocytes, RNA, Messenger, Reactive Oxygen Species, Chemokine CCL2, Neutrophil Infiltration, Mice, Nitric Oxide Synthase Type II, Nuclear Receptor Subfamily 1, Group F, Member 3, Arterial Pressure
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