Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension

Sabine Kossmann; Jeremy Lagrange; Sven Jäckel; Kerstin Jurk; Moritz Ehlken; Tanja Schönfelder; Yvonne Weihert; Maike Knorr; Moritz Brandt; Ning Xia; Huige Li; Andreas Daiber; Matthias Oelze; Christoph Reinhardt; Karl Lackner; Andras Gruber; Brett Monia; Susanne H. Karbach; Ulrich Walter; Zaverio M. Ruggeri; Thomas Renné; Wolfram Ruf; Thomas Münzel; Philip Wenzel

doi:10.1126/scitranslmed.aah4923

Research ArticleHypertension

Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension

Sabine Kossmann¹,²,*,
Jeremy Lagrange¹,*,
Sven Jäckel¹,†,
Kerstin Jurk¹,†,
Moritz Ehlken¹,²,†,
Tanja Schönfelder¹,
Yvonne Weihert²,
Maike Knorr²,
Moritz Brandt²,
Ning Xia³,
Huige Li³,
Andreas Daiber²,
Matthias Oelze²,
Christoph Reinhardt¹,
Karl Lackner⁴,
Andras Gruber⁵,⁶,
Brett Monia⁷,
Susanne H. Karbach²,
Ulrich Walter¹,
Zaverio M. Ruggeri⁸,
Thomas Renné⁹,¹⁰,
Wolfram Ruf¹,¹¹,¹²,
Thomas Münzel²,¹² and
Philip Wenzel¹,²,¹²,‡

¹Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.
²Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.
³Department of Pharmacology, University Medical Center Mainz, 55131 Mainz, Germany.
⁴Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, 55131 Mainz, Germany.
⁵Department of Biomedical Engineering, Oregon Health and Science University, 3303 Southwest Bond Avenue, CH13B, Portland, OR 97239, USA.
⁶Aronora Inc., 4640 Southwest Macadam Avenue, Suite 200A, Portland, OR 97239, USA.
⁷Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.
⁸Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
⁹Department of Molecular Medicine and Surgery, L1:00, Karolinska Institutet, SE-171 71 Stockholm, Sweden.
¹⁰Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
¹¹Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.
¹²DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, University Medical Center Mainz, 55131 Mainz, Germany.

↵‡Corresponding author. Email: wenzelp{at}uni-mainz.de

↵* These authors contributed equally as first authors.
↵† These authors contributed equally as second authors.

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Science Translational Medicine 01 Feb 2017:
Vol. 9, Issue 375, eaah4923
DOI: 10.1126/scitranslmed.aah4923

Sabine Kossmann

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Jeremy Lagrange

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

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Sven Jäckel

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

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Kerstin Jurk

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

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Moritz Ehlken

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Tanja Schönfelder

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

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Yvonne Weihert

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.

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Maike Knorr

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.

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Moritz Brandt

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.

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Ning Xia

Department of Pharmacology, University Medical Center Mainz, 55131 Mainz, Germany.

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Huige Li

Department of Pharmacology, University Medical Center Mainz, 55131 Mainz, Germany.

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Andreas Daiber

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.

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Matthias Oelze

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.

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Christoph Reinhardt

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

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Karl Lackner

Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, 55131 Mainz, Germany.

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Andras Gruber

Department of Biomedical Engineering, Oregon Health and Science University, 3303 Southwest Bond Avenue, CH13B, Portland, OR 97239, USA.Aronora Inc., 4640 Southwest Macadam Avenue, Suite 200A, Portland, OR 97239, USA.

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Brett Monia

Ionis Pharmaceuticals Inc., 2855 Gazelle Court, Carlsbad, CA 92010, USA.

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Susanne H. Karbach

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.

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Ulrich Walter

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

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Zaverio M. Ruggeri

Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

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Thomas Renné

Department of Molecular Medicine and Surgery, L1:00, Karolinska Institutet, SE-171 71 Stockholm, Sweden.Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.

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Wolfram Ruf

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA.DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, University Medical Center Mainz, 55131 Mainz, Germany.

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Thomas Münzel

Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, University Medical Center Mainz, 55131 Mainz, Germany.

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Philip Wenzel

Center for Thrombosis and Hemostasis Mainz, University Medical Center Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.Center for Cardiology, Cardiology I, University Medical Center Mainz, 55131 Mainz, Germany.DZHK (German Center for Cardiovascular Research), Partner Site Rhine Main, University Medical Center Mainz, 55131 Mainz, Germany.

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For correspondence: wenzelp@uni-mainz.de

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Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension

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