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Publication : Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer.

First Author  Malehmir M Year  2019
Journal  Nat Med Volume  25
Issue  4 Pages  641-655
PubMed ID  30936549 Mgi Jnum  J:298790
Mgi Id  MGI:6488692 Doi  10.1038/s41591-019-0379-5
Citation  Malehmir M, et al. (2019) Platelet GPIbalpha is a mediator and potential interventional target for NASH and subsequent liver cancer. Nat Med 25(4):641-655
abstractText  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 GPIbalpha 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.
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