{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:32:02Z","timestamp":1787790722049,"version":"build-2784847793"},"reference-count":47,"publisher":"Georg Thieme Verlag KG","issue":"12","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81870106"],"award-info":[{"award-number":["81870106"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82070138"],"award-info":[{"award-number":["82070138"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82000139"],"award-info":[{"award-number":["82000139"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81930042"],"award-info":[{"award-number":["81930042"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81730047"],"award-info":[{"award-number":["81730047"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82025017"],"award-info":[{"award-number":["82025017"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004731","name":"Zhejiang Provincial Natural Science Foundation","doi-asserted-by":"crossref","award":["LZ23H080001"],"award-info":[{"award-number":["LZ23H080001"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Innovation Institute of Basic Medical Sciences, Zhejiang University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:p>\n            Introduction\u2003Platelets link thrombosis and inflammation, but how platelets handle the endogenous intraplatelet inflammatory machinery is less well understood. NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) is the central component of the interleukin (IL)-1-producing inflammasome. Elucidating the cell type-specific mechanism of NLRP3 in platelets may improve our understanding of thrombotic diseases.<\/jats:p><jats:p>\n            Methods\u2003Ferric chloride-induced mesenteric arteriole thrombosis models, tail bleeding models, and microfluidic whole-blood perfusion were used to study thrombosis and hemostasis. Additionally, we utilized aggregometry, flow cytometry, immunoprecipitation, and western blotting to investigate glycoprotein (GP)Ib-IX-mediated platelet function and signaling.<\/jats:p><jats:p>\n            Results\u2003NLRP3\u2212\/\u2212 mice exhibited severely impaired thrombosis and hemostasis, whereas apoptosis-associated speck-like protein containing a CARD (ASC)\u2212\/\u2212, caspase-1\u2212\/\u2212, and Nlrp3\n            A350V\/+\n            CrePF4 mice did not exhibit such changes. NLRP3\u2212\/\u2212 platelets exhibited reduced adhesion to injured vessel walls and collagen and impaired von Willebrand factor (vWF)-dependent translocation and rolling behavior. NLRP3 deficiency decreased botrocetin-induced platelet aggregation and the phosphorylation of key signaling molecules in the GPIb-IX pathway. Mechanistically, decreased cAMP\/PKA activity led to reduced phosphorylation of NLRP3, thereby enabling the interaction between NLRP3 and filamin A. This interaction accelerated the dissociation of filamin A from GPIb\u03b1, which allowed a 14\u20133-3\u03b6-dependent increase in GPIb-IX affinity to vWF. Finally, platelet NLRP3 was found to largely regulate thrombotic disease models, such as models of stroke and deep vein thrombosis.<\/jats:p><jats:p>\n            Conclusion\u2003NLRP3 promoted the function of the major platelet adhesion receptor GPIb-IX without involving NLRP3 inflammasome assembly or IL-1\u03b2 production.<\/jats:p>","DOI":"10.1055\/a-2263-8372","type":"journal-article","created":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T23:51:20Z","timestamp":1707349880000},"page":"1095-1113","source":"Crossref","is-referenced-by-count":13,"title":["Inflammasome-Independent Mechanism of NLRP3 is Critical for Platelet GPIb-IX Function and Thrombosis"],"prefix":"10.1055","volume":"124","author":[{"given":"Xiaoyan","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingke","family":"Li","sequence":"first","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangfan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery, The Center for Integrated Oncology and Precision Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingqi","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yilin","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology and Bone Marrow Transplantation Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Institute of Hematology, Zhejiang University & Zhejiang Engineering Laboratory for Stem Cell and Immunotherapy, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cell Biology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"},{"name":"Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2712-1705","authenticated-orcid":false,"given":"Di","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Department of Orthopaedic Surgery of the Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People's Republic of 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