Thrombosis and Haemostasis, Table of Contents Thromb Haemost 2024; 124(12): 1114-1116DOI: 10.1055/a-2413-4672 Invited Editorial Focus NLRP3: More than an Inflammasome? Gabrielle J. Pennings 1 ANZAC Research Institute-Sydney Local Health District, The University of Sydney, Concord NSW, Australia › Author Affiliations Recommend Article Abstract Buy Article Comment to this article: Inflammasome-Independent Mechanism of NLRP3 is Critical for Platelet GPIb-IX Function and ThrombosisThromb Haemost 2024; 124(12): 1095-1113DOI: 10.1055/a-2263-8372 Full Text References References 1 Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002; 10 (02) 417-426 2 Aganna E, Martinon F, Hawkins PN. et al. Association of mutations in the NALP3/CIAS1/PYPAF1 gene with a broad phenotype including recurrent fever, cold sensitivity, sensorineural deafness, and AA amyloidosis. Arthritis Rheum 2002; 46 (09) 2445-2452 3 Manji GA, Wang L, Geddes BJ. et al. PYPAF1, a PYRIN-containing Apaf1-like protein that assembles with ASC and regulates activation of NF-kappa B. J Biol Chem 2002; 277 (13) 11570-11575 4 Grebe A, Hoss F, Latz E. NLRP3 inflammasome and the IL-1 pathway in atherosclerosis. Circ Res 2018; 122 (12) 1722-1740 5 Toldo S, Abbate A. The role of the NLRP3 inflammasome and pyroptosis in cardiovascular diseases. Nat Rev Cardiol 2024; 21 (04) 219-237 6 McManus RM, Latz E. NLRP3 inflammasome signalling in Alzheimer's disease. Neuropharmacology 2024; 252: 109941 7 Liang R, Qi X, Cai Q. et al. The role of NLRP3 inflammasome in aging and age-related diseases. Immun Ageing 2024; 21 (01) 14 8 Bourne JH, Campos J, Hopkin SJ. et al. Megakaryocyte NLRP3 hyperactivation induces mild anemia and potentiates inflammatory response in mice. Front Immunol 2023; 14: 1226196 9 Chen X, Li J, Liu P. et al. Inflammasome-independent mechanism of NLRP3 is critical for platelet GPIb-IX function and thrombosis. Thromb Haemost 2024; 124 (12) 1095-1113 10 Hottz ED, Lopes JF, Freitas C. et al. Platelets mediate increased endothelium permeability in dengue through NLRP3-inflammasome activation. Blood 2013; 122 (20) 3405-3414 11 Murthy P, Durco F, Miller-Ocuin JL. et al. The NLRP3 inflammasome and bruton's tyrosine kinase in platelets co-regulate platelet activation, aggregation, and in vitro thrombus formation. Biochem Biophys Res Commun 2017; 483 (01) 230-236 12 Pennings GJ, Reddel CJ, Traini M. et al. Rapid release of interleukin-1β from human platelets is independent of NLRP3 and caspase. Thromb Haemost 2022; 122 (04) 517-528 13 Qiao J, Wu X, Luo Q. et al. NLRP3 regulates platelet integrin αIIbβ3 outside-in signaling, hemostasis and arterial thrombosis. Haematologica 2018; 103 (09) 1568-1576 14 Su M, Chen C, Li S. et al. Gasdermin D-dependent platelet pyroptosis exacerbates NET formation and inflammation in severe sepsis. Nat Cardiovasc Res 2022; 1 (08) 732-747 15 Vogel S, Arora T, Wang X. et al. The platelet NLRP3 inflammasome is upregulated in sickle cell disease via HMGB1/TLR4 and Bruton tyrosine kinase. Blood Adv 2018; 2 (20) 2672-2680 16 Vogel S, Murthy P, Cui X, Lotze MT, Zeh III HJ, Sachdev U. TLR4-dependent upregulation of the platelet NLRP3 inflammasome promotes platelet aggregation in a murine model of hindlimb ischemia. Biochem Biophys Res Commun 2019; 508 (02) 614-619 17 Corcoran SE, Halai R, Cooper MA. Pharmacological inhibition of the nod-like receptor family pyrin domain containing 3 inflammasome with MCC950. Pharmacol Rev 2021; 73 (03) 968-1000 18 Ma Q. Pharmacological inhibition of the NLRP3 inflammasome: structure, molecular activation, and inhibitor-NLRP3 interaction. Pharmacol Rev 2023; 75 (03) 487-520 19 Coll RC, Hill JR, Day CJ. et al. MCC950 directly targets the NLRP3 ATP-hydrolysis motif for inflammasome inhibition. Nat Chem Biol 2019; 15 (06) 556-559 20 Ridker PM, Everett BM, Thuren T. et al; CANTOS Trial Group. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med 2017; 377 (12) 1119-1131 21 Hettwer J, Hinterdobler J, Miritsch B. et al. Interleukin-1β suppression dampens inflammatory leucocyte production and uptake in atherosclerosis. Cardiovasc Res 2022; 118 (13) 2778-2791