title: Gut Microbiota Promote Angiotensin II-Induced Arterial Hypertension and Vascular Dysfunction.
abstract: 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.
  
  
  
  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 (AngII; 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 AngII. Importantly, cardiac inflammation, fibrosis and systolic dysfunction were attenuated in GF mice, indicating systemic protection from cardiovascular inflammatory stress induced by AngII.
  
  
  
  Gut microbiota facilitate AngII-induced vascular dysfunction and hypertension, at least in part, by supporting an MCP-1/IL-17 driven vascular immune cell infiltration and inflammation.
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany.
authors: Susanne H
authors: SH
authors: Karbach
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Tanja
authors: T
authors: Schönfelder
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Ines
authors: I
authors: Brandão
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Eivor
authors: E
authors: Wilms
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Nives
authors: N
authors: Hörmann
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Sven
authors: S
authors: Jäckel
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Institute of Molecular Medicine, University Medical Center Mainz, Mainz, Germany.
authors: Rebecca
authors: R
authors: Schüler
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Stefanie
authors: S
authors: Finger
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany.
authors: Maike
authors: M
authors: Knorr
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany.
authors: Jeremy
authors: J
authors: Lagrange
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany.
authors: Moritz
authors: M
authors: Brandt
authors: Institute of Molecular Medicine, University Medical Center Mainz, Mainz, Germany.
authors: Ari
authors: A
authors: Waisman
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany.
authors: Sabine
authors: S
authors: Kossmann
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany.
authors: Katrin
authors: K
authors: Schäfer
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany.
authors: Thomas
authors: T
authors: Münzel
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany.
authors: Christoph
authors: C
authors: Reinhardt
authors: Center for Thrombosis and Hemostasis Mainz, Partner Site RheinMain, Mainz, Germany Center for Cardiology, Partner Site RheinMain, Mainz, Germany German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany wenzelp@uni-mainz.de.
authors: Philip
authors: P
authors: Wenzel
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D062186:Arterial Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000187:drug effects / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000187:drug effects / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D005856:Germ-Free Life; D006973:Hypertension / Q000382:microbiology; D007962:Leukocytes / Q000187:drug effects*; D051379:Mice; D009000:Monocytes; D000074662:NADPH Oxidase 2 / Q000187:drug effects / Q000235:genetics; D020556:Neutrophil Infiltration / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D000804:Angiotensin II; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C488842:Cybb protein, mouse; D000074662:NADPH Oxidase 2
keywords: angiotensin II; arterial hypertension; gut microbiota; inflammation; monocytes; vascular dysfunction