{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:43:32Z","timestamp":1793029412409,"version":"4.5.0"},"reference-count":22,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002996","name":"Hartstichting","doi-asserted-by":"publisher","award":["03\u2010003\u20102023\u20100080"],"award-info":[{"award-number":["03\u2010003\u20102023\u20100080"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pulmonary arterial hypertension (PAH) is a progressive vasculopathy leading to right\u2010sided heart failure. We have shown previously that the (NOD\u2010like\u2010receptor\u20103) NLRP3 inflammasome is activated in end\u2010stage disease of the monocrotaline and aortocaval shunt (MCT\/ACS) neointimal PAH rat model. The NLRP3 and absent\u2010in\u2010melanoma 2 (AIM2) inflammasomes mediate the secretion of interleukin (IL)\u20101\u03b2 and IL\u201018. We investigated the role of the NLRP3 inflammasome in PAH rats and the presence of NLRP3 and AIM2 in PAH rat and pediatric patient lungs. For a natural history study, we assessed inflammasome activation by Western blot at different disease stages in the MCT\/ACS neointimal PAH rat model. To assess the role of the inflammasome in PAH, we treated PAH rats with or without the NLRP3 inflammasome inhibitor MCC950 and assessed vascular remodeling employing hematoxylin and eosin staining on rat lungs. Lung sections from patients who had undergone lung transplantation were stained for NLRP3 and AIM2 using immunofluorescence. We found that inflammasome activation in lungs of PAH rats, reflected by cleaved caspase\u20101, IL\u20101\u03b2, and IL\u201018, increased over time, reaching significance for cleaved caspase\u20101 and IL\u201018 in end\u2010stage PAH. The NLRP3 inflammasome inhibitor MCC950 suppressed vascular remodeling but not hemodynamic variables compared to control PAH rats. We detected NLRP3\n                    <jats:sup>+<\/jats:sup>\n                    and AIM2\n                    <jats:sup>+<\/jats:sup>\n                    cells in end\u2010stage pediatric PAH lungs. In conclusion, inflammasome activation increases over time in the MCT\/ACS neointimal PAH rat model, and NLRP3 inflammasome activation increases vascular remodeling. NLRP3 and AIM2 positive cells are present in end\u2010stage pediatric patient PAH lungs, suggesting human relevance.\n                  <\/jats:p>","DOI":"10.1002\/pul2.70354","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T15:44:58Z","timestamp":1784303098000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The NLRP3 Inflammasome Increases Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2635-1998","authenticated-orcid":false,"given":"Emmanouil","family":"Mavrogiannis","sequence":"first","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital University Medical Center Groningen, University of Groningen Groningen the Netherlands"},{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca","family":"Weldeghebreal","sequence":"additional","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris R.","family":"Schilthuis","sequence":"additional","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain K.","family":"Fal","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels J.","family":"Kloosterhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam H.","family":"Koster","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim","family":"Timens","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes M.","family":"Douwes","sequence":"additional","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4385-5784","authenticated-orcid":false,"given":"Rolf M. F.","family":"Berger","sequence":"additional","affiliation":[{"name":"Center for Congenital Heart Diseases, Department of Pediatric Cardiology, Beatrix Children's Hospital University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit","family":"Westerterp","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical Center Groningen, University of Groningen Groningen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000329"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01916-2018"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.58.6.1107"},{"issue":"1","key":"e_1_2_10_5_1","first-page":"70","article-title":"Plexogenic Pulmonary Arteriopathy. Significance of Medial Thickness With Respect to Advanced Pulmonary Vascular Lesions","volume":"105","author":"Yamaki S.","year":"1981","journal-title":"American Journal of Pathology"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301141"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/pul2.12101"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1707914"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2012.04.008"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.933762"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01448-2015"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.151.5.7735624"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202110-2274OC"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307634"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033098"},{"issue":"55065","key":"e_1_2_10_16_1","first-page":"1","article-title":"Shunt Surgery, Right Heart Catheterization, and Vascular Morphometry in a Rat Model for Flow\u2010Induced Pulmonary Arterial Hypertension","volume":"120","author":"Van Der Feen D. E.","year":"2017","journal-title":"Journal of Visualized Experiments: JoVE"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaw4974"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-025-02230-7"},{"issue":"3","key":"e_1_2_10_19_1","first-page":"248","article-title":"A Small\u2010Molecule Inhibitor of the NLRP3 Inflammasome for the Treatment of Inflammatory Diseases","volume":"21","author":"Coll R. C.","year":"2015","journal-title":"Nature Medicine (New York, NY, United States)"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.319971"},{"issue":"1","key":"e_1_2_10_21_1","first-page":"1","article-title":"Animal Models of PAH and Increased Pulmonary Blood Flow","volume":"1","author":"Dickinson M. G.","year":"2021","journal-title":"Pediatr Congenit Cardiol Card Surg Intensive Care"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000171"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00035607"}],"container-title":["Pulmonary Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pul2.70354","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pul2.70354","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pul2.70354","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:32:01Z","timestamp":1793028721000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pul2.70354"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":22,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/pul2.70354"],"URL":"https:\/\/doi.org\/10.1002\/pul2.70354","archive":["Portico"],"relation":{},"ISSN":["2045-8940","2045-8940"],"issn-type":[{"value":"2045-8940","type":"print"},{"value":"2045-8940","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"assertion":[{"value":"2026-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70354"}}