2026-06-14T02:28:44Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/179572024-11-29T22:14:16Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud author Malehmir, Mohsen author Pfister, Dominik author Gallage, Suchira author Szydlowska, Marta author Inverso, Donato author Kotsiliti, Elena author Leone, Valentina author Peiseler, Moritz author Surewaard, Bas G J author Rath, Dominik author Ali, Adnan author Wolf, Monika Julia author Drescher, Hannah author Healy, Marc E author Dauch, Daniel author Kroy, Daniela author Krenkel, Oliver author Kohlhepp, Marlene author Engleitner, Thomas author Olkus, Alexander author Sijmonsma, Tjeerd author Volz, Julia author Deppermann, Carsten author Stegner, David author Helbling, Patrick author Nombela-Arrieta, César author Rafiei, Anahita author Hinterleitner, Martina author Rall, Marcel author Baku, Florian author Borst, Oliver author Wilson, Caroline L author Leslie, Jack author O'Connor, Tracy author Weston, Christopher J author Chauhan, Abhishek author Adams, David H author Sheriff, Lozan author Teijeiro, Ana author Prinz, Marco author Bogeska, Ruzhica author Anstee, Natasha author Bongers, Malte N author Notohamiprodjo, Mike author Geisler, Tobias author Withers, Dominic J author Ware, Jerry author Mann, Derek A author Augustin, Hellmut G author Vegiopoulos, Alexandros author Milsom, Michael D author Rose, Adam J author Lalor, Patricia F author Llovet, Josep M author Pinyol, Roser author Tacke, Frank author Rad, Roland author Matter, Matthias author Djouder, Nabil author Kubes, Paul author Knolle, Percy A author Unger, Kristian author Zender, Lars author Nieswandt, Bernhard author Gawaz, Meinrad author Weber, Achim author Heikenwalder, Mathias funder University of Zurich (Suiza) funder Hartmann Müller Foundation funder Helmholtz-Gemeinschaft, Zukunftsthema 'Immunology and Inflammation funder Leibniz Association funder Unión Europea. Comisión Europea. Joint Research Centre (JRC) funder Swiss National Science Foundation funder Unión Europea. Comisión Europea. European Research Council (ERC) funder Research Foundation - Flanders funder German Cancer Aid funder Federal Ministry of Education & Research (Alemania) funder European Molecular Biology Organization funder Asociación Española Contra el Cáncer funder Government of Catalonia (España) funder United States Department of Health and Human Services funder UK Research and Innovation funder Deutsche Forschungsgemeinschaft (Alemania) 2024-02-12T10:55:28Z 2024-02-12T10:55:28Z 2019-04 Nat Med . 2019 ;25(4):641-655. 10.1038/s41591-019-0379-5 1546-170X Nature medicine 30936549 http://hdl.handle.net/20.500.12105/17957 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. eng Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer. journal article 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 URL https://repisalud.isciii.es/bitstreams/d544d5b0-7cd1-4025-ae5b-a55a86f12aac/download File MD5 3821fcd1dc3ed1c30bef2b6917d6a773 1152769 application/pdf PlateletGPIbisamediatopotential-2019.pdf URL https://repisalud.isciii.es/bitstreams/8cf3efd8-84fc-45ff-a2d9-a6cd99efd157/download File MD5 0abe7afbe5aef5303080babb0dee0920 8487946 application/pdf PlateletGPIbisamediatopotential-figures-2019.pdf URL https://repisalud.isciii.es/bitstreams/8bee4915-9eae-44aa-aada-9816542608da/download File MD5 4e510273ba1a44883495f7979420380f 66943 text/plain PlateletGPIbisamediatopotential-2019.pdf.txt URL https://repisalud.isciii.es/bitstreams/e247742a-f332-4e59-999e-6c5d73b32683/download File MD5 6d93d3216dc4a7f5df47d4876fbec4d3 6 text/plain PlateletGPIbisamediatopotential-figures-2019.pdf.txt