Beschreibung:
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<jats:bold>Background:</jats:bold>
The presence of gut microbiota is essential for proper function of the immune cells. Its impact on the blood pressure regulation and systemic vascular function - processes that are described to be immune cell regulated - is unknown.
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<jats:bold>Methods and Results:</jats:bold>
Unchallenged germfree mice (GF) showed no differences in endothelial function or vascular oxidative stress compared to conventionally reared mice (CONV-R), but they provided a dampened systemic T-bet / Interferon gamma (IFNγ) skewing in lymphoid cells. Re-colonization of GF with regular gut microbiota (conventionally-derived, CONV-D) normalized this phenotype. Angiotensin II (1mg/kg/d for 7d)-infused GF mice showed reduced oxidative stress levels in the vasculature, attenuated vascular expression of monocyte chemoattractant protein-1 and iNOS, blocked systemic up-regulation of T-bet / IFNγ and retinoic-acidreceptor-related orphan receptor-γt (ROR-γt) / interleukin-17 (IL-17) signaling in lymphoid cells and protection from endothelial dysfunction compared to CONV-R mice. Flow cytometric analysis showed a reduced infiltration of Ly6G+ neutrophils into the vessel wall and consequently we found an attenuation of arterial hypertension in Angiotensin II infused GF mice compared to Angiotensin II infused CONV-R mice. Protection from Angiotensin II induced vascular injury and the IFNγ / Ly6C+ monocyte axis as well as the IL-17/Ly6G+ axis was reversed in CONV-D mice.
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<jats:bold>Conclusion:</jats:bold>
Gut microbiota seem to facilitate Angiotensin II induced hypertension by supporting a T-bet / IFNγ and ROR-γt / IL-17 driven vascular inflammation with infiltration of Ly6G+ neutrophils.
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