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http://purl.uniprot.org/citations/30936549http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/30936549http://www.w3.org/2000/01/rdf-schema#comment"Non-alcoholic fatty liver disease ranges from steatosis to non-alcoholic steatohepatitis (NASH), potentially progressing to cirrhosis and hepatocellular carcinoma (HCC). Here, we show that platelet number, platelet activation and platelet aggregation are increased in NASH but not in steatosis or insulin resistance. Antiplatelet therapy (APT; aspirin/clopidogrel, ticagrelor) but not nonsteroidal anti-inflammatory drug (NSAID) treatment with sulindac prevented NASH and subsequent HCC development. Intravital microscopy showed that liver colonization by platelets depended primarily on Kupffer cells at early and late stages of NASH, involving hyaluronan-CD44 binding. APT reduced intrahepatic platelet accumulation and the frequency of platelet-immune cell interaction, thereby limiting hepatic immune cell trafficking. Consequently, intrahepatic cytokine and chemokine release, macrovesicular steatosis and liver damage were attenuated. Platelet cargo, platelet adhesion and platelet activation but not platelet aggregation were identified as pivotal for NASH and subsequent hepatocarcinogenesis. In particular, platelet-derived GPIbα proved critical for development of NASH and subsequent HCC, independent of its reported cognate ligands vWF, P-selectin or Mac-1, offering a potential target against NASH."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.org/dc/terms/identifier"doi:10.1038/s41591-019-0379-5"xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Ali A."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Rad R."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Volz J."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Weber A."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Ware J."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Knolle P.A."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Nieswandt B."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Gawaz M."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"O'Connor T."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Chauhan A."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Augustin H.G."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Matter M."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Dauch D."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Zender L."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Leslie J."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Adams D.H."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Lalor P.F."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Wilson C.L."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Pinyol R."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Kubes P."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Heikenwalder M."xsd:string
http://purl.uniprot.org/citations/30936549http://purl.uniprot.org/core/author"Rose A.J."xsd:string