title: Role of the receptor Mas in macrophage-mediated inflammation in vivo.
abstract: Recently, an alternative renin-angiotensin system pathway has been described, which involves binding of angiotensin-(1-7) to its receptor Mas. The Mas axis may counterbalance angiotensin-II-mediated proinflammatory effects, likely by affecting macrophage function. Here we investigate the role of Mas in murine models of autoimmune neuroinflammation and atherosclerosis, which both involve macrophage-driven pathomechanisms. Mas signaling affected macrophage polarization, migration, and macrophage-mediated T-cell activation. Mas deficiency exacerbated the course of experimental autoimmune encephalomyelitis and increased macrophage infiltration as well as proinflammatory gene expression in the spleen and spinal cord. Furthermore, Mas deficiency promoted atherosclerosis by affecting macrophage infiltration and migration and led to increased oxidative stress as well as impaired endothelial function in ApoE-deficient mice. In summary, we identified the Mas axis as an important factor in macrophage function during inflammation of the central nervous and vascular system in vivo. Modulating the Mas axis may constitute an interesting therapeutic target in multiple sclerosis and/or atherosclerosis.
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Hammer
authors.affiliation: Department of Nephrology, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Friedrich
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Kovacs
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: De-Hyung
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Nephrology, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Grave
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jörg
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.affiliation: Department of Molecular Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Janina
authors.initials: J
authors.lastname: Grosch
authors.affiliation: Department of Molecular Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Winkler
authors.affiliation: Department of Neurology, Ruhr-University Bochum, 44801 Bochum, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Gold
authors.affiliation: Charité-University Medicine, 10117 Berlin, Germany.|German Center for Cardiovascular Research, Partner Site Berlin, 13347 Berlin, Germany.|Institute for Biology, University of Lübeck, 23538 Lübeck, Germany.|Experimental and Clinical Research Center, a joint cooperation of Max Delbrück Center for Molecular Medicine and Charité Medical Faculty, 13125 Berlin, Germany.|Berlin Institute of Health, 10117 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Manzel
authors.affiliation: Department of Nephrology, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany.
authors.forename: Lars C
authors.initials: LC
authors.lastname: Rump
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.|Institute for Biology, University of Lübeck, 23538 Lübeck, Germany.
authors.forename: Dominik N
authors.initials: DN
authors.lastname: Müller
authors.affiliation: Department of Neurology, Friedrich-Alexander-University Erlangen-Nuremberg, 91054 Erlangen, Germany; ralf.linker@uk-erlangen.de johannes.stegbauer@med.uni-duesseldorf.de.
authors.forename: Ralf A
authors.initials: RA
authors.lastname: Linker
authors.affiliation: Department of Nephrology, Medical Faculty, Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, Germany; ralf.linker@uk-erlangen.de johannes.stegbauer@med.uni-duesseldorf.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Stegbauer
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D015870:Gene Expression; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013601:T-Lymphocytes / Q000502:physiology
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled
keywords: EAE; atherosclerosis; inflammation; macrophages; renin–angiotensin system