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Hamostaseologie 2019; 39(02): 173-179
DOI: 10.1055/s-0038-1675357
Review Article
Georg Thieme Verlag KG Stuttgart · New York

The Gut Microbiota as an Influencing Factor of Arterial Thrombosis

Christoph Reinhardt
1   Center for Thrombosis and Hemostasis (CTH), University Medical Center Mainz, Johannes Gutenberg University of Mainz, Mainz, Germany
2   German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Mainz, Germany
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Further Information

Publication History

03 July 2018

17 September 2018

Publication Date:
20 November 2018 (online)

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Abstract

The mutualistic gut microbiota does not only impact the development and function of various immune cell types, but it also influences the function of the hepatic vascular endothelium and prothrombotic platelet function. With germ-free mouse models, we have demonstrated that gut-derived microbial-associated molecular patterns could stimulate hepatic von Willebrand factor (VWF) synthesis and plasmatic VWF levels through Toll-like receptor-2 (TLR2), thus defining the extent of platelet deposition to the subendothelial matrix of the ligation-injured common carotid artery. In addition to the microbiota-derived choline metabolite trimethylamine N-oxide and the microbiota's regulatory role on the colonic serotonin biosynthesis pathway, affecting prothrombotic platelet function, TLR2-regulated hepatic endothelial VWF synthesis and elevated VWF plasma levels constitute a pivotal mechanism of how the gut microbiota is linked to arterial thrombosis. Conceptually, in addition to the identified functions of the gut microbiota in modulating host nutrition and metabolism, our work places the innate immune functions of the liver sinusoidal endothelium as an actuating variable in arterial thrombus growth.

Zusammenfassung

Die mutualistische Darm-Mikrobiota beeinflusst nicht nur die Entwicklung und Funktion verschiedener Immunzelltypen, sondern auch die hepatische Endothel- und prothrombotische Thrombozytenfunktion. Mit keimfreien Mausmodellen haben wir gezeigt, dass aus dem Darm stammende mikrobiell assoziierte molekulare Muster die Synthese den hepatischen Von-Willebrand-Faktors (VWF) und den plasmatischen VWF durch dem Toll-like-Rezeptor-2 (TLR2) stimulieren und so das Ausmaß der Thrombozytenablagerung an die subendotheliale Matrix der durch Ligatur verletzten Arteria carotis communis bestimmen. Zusätzlich zu dem von der Mikrobiota stammenden Cholin-Metaboliten Trimethylamin-N-Oxid und der regulatorischen Wirkung der Mikrobiota auf den Serotonin-Biosyntheseweg im Kolon, welche die Thrombozytenfunktion beeinflussen, bilden die TLR2-regulierte endotheliale VWF-Synthese in der Leber und erhöhte VWF-Plasmaspiegel eine zentrale Verbindung zwischen Darmmikrobiota und arterieller Thrombose. Neben den identifizierten Einflüssen der Darmmikrobiota auf die Ernährung und den Wirtsmetabolismus legt unsere Arbeit konzeptuell die angeborenen Immunfunktionen den sinusoidalen Leberendothels als Stellgröße des arteriellen Thrombuswachstums fest.

Keywords

microbiota - germ-free - coagulation - thrombosis

Schlüsselwörter

Mikrobiota - keimfrei - Gerinnung - Thrombose
 

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