Abstract 17805: Gut Microbiota Promote Arterial Hypertension and Vascular Dysfunction by Facilitating Remote Interleukin-17 Signaling
Background: 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.
Methods and Results: 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.
Conclusion: 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.
Author Disclosures: S. Karbach: None. N. Hörmann: None. S. Jäckel: None. T. Schönfelder: None. R. Schüler: None. S. Finger: None. M. Knorr: None. S. Kossmann: None. M. Brandt: None. T. Münzel: None. F. Bäckhed: None. C. Reinhardt: None. P. Wenzel: None.
- © 2015 by American Heart Association, Inc.