{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:38:01Z","timestamp":1790116681745,"version":"4.0.1"},"reference-count":41,"publisher":"Elsevier BV","issue":"1","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["P30 AR070254"],"award-info":[{"award-number":["P30 AR070254"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007880","name":"Johns Hopkins University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007880","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K24 AR080217"],"award-info":[{"award-number":["K24 AR080217"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["K23HL153781"],"award-info":[{"award-number":["K23HL153781"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R03HL176624"],"award-info":[{"award-number":["R03HL176624"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chestpulmonary.org","clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["CHEST Pulmonary"],"published-print":{"date-parts":[[2026,3]]},"DOI":"10.1016\/j.chpulm.2025.100212","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T01:51:45Z","timestamp":1757555505000},"page":"100212","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased Xanthine Oxidoreductase Activity in Patients With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension"],"prefix":"10.1016","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4847-6876","authenticated-orcid":false,"given":"Julie C.","family":"Coursen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tijana","family":"Tuhy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrianne","family":"Woods","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura K.","family":"Hummers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ami A.","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Hassoun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel L.","family":"Damico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen C.","family":"Mathai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine E.","family":"Simpson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"25","key":"10.1016\/j.chpulm.2025.100212_bib1","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1056\/NEJMra2000348","article-title":"Pulmonary arterial hypertension","volume":"385","author":"Hassoun","year":"2021","journal-title":"N Engl J Med"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib2","doi-asserted-by":"crossref","DOI":"10.1186\/s42358-022-00239-2","article-title":"Increased risk of mortality in systemic sclerosis-associated pulmonary hypertension: a systemic review and meta-analysis","volume":"62","author":"Xiong","year":"2022","journal-title":"Adv Rheumatol"},{"issue":"9","key":"10.1016\/j.chpulm.2025.100212_bib3","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1002\/art.22069","article-title":"Clinical differences between idiopathic and scleroderma-related pulmonary hypertension","volume":"54","author":"Fisher","year":"2006","journal-title":"Arthritis Rheum"},{"issue":"9","key":"10.1016\/j.chpulm.2025.100212_bib4","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1164\/rccm.201507-1456OC","article-title":"Comparison of treatment response in idiopathic and connective tissue disease-associated pulmonary arterial hypertension","volume":"192","author":"Rhee","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"10.1016\/j.chpulm.2025.100212_bib5","doi-asserted-by":"crossref","DOI":"10.1177\/2045894019859477","article-title":"Serum uric acid as a marker of disease risk, severity, and survival in systemic sclerosis-related pulmonary arterial hypertension","volume":"9","author":"Simpson","year":"2019","journal-title":"Pulm Circ"},{"issue":"7","key":"10.1016\/j.chpulm.2025.100212_bib6","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1136\/annrheumdis-2013-203301","article-title":"Evidence-based detection of pulmonary arterial hypertension in systemic sclerosis: the DETECT study","volume":"73","author":"Coghlan","year":"2014","journal-title":"Ann Rheum Dis"},{"issue":"2","key":"10.1016\/j.chpulm.2025.100212_bib7","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00332-2020","article-title":"Serum and pulmonary uric acid in pulmonary arterial hypertension","volume":"58","author":"Savale","year":"2021","journal-title":"Eur Respir J"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib8","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1378\/chest.117.1.19","article-title":"Hyperuricemia in severe pulmonary hypertension","volume":"117","author":"Voelkel","year":"2000","journal-title":"Chest"},{"issue":"2","key":"10.1016\/j.chpulm.2025.100212_bib9","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1164\/ajrccm.160.2.9812078","article-title":"Serum uric acid levels correlate with the severity and the mortality of primary pulmonary hypertension","volume":"160","author":"Nagaya","year":"1999","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"10.1016\/j.chpulm.2025.100212_bib10","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/j.healun.2014.01.853","article-title":"Endothelin antagonism and uric acid levels in pulmonary arterial hypertension: clinical associations","volume":"33","author":"Dhaun","year":"2014","journal-title":"J Heart Lung Transplant"},{"key":"10.1016\/j.chpulm.2025.100212_bib11","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ijcard.2015.08.109","article-title":"Regulation of uric acid metabolism and excretion","volume":"213","author":"Maiuolo","year":"2016","journal-title":"Int J Cardiol"},{"issue":"8","key":"10.1016\/j.chpulm.2025.100212_bib12","doi-asserted-by":"crossref","first-page":"4985","DOI":"10.1074\/jbc.274.8.4985","article-title":"Binding of xanthine oxidase to vascular endothelium: kinetic characterization and oxidative impairment of nitric oxide-dependent signaling","volume":"274","author":"Houston","year":"1999","journal-title":"J Biol Chem"},{"key":"10.1016\/j.chpulm.2025.100212_bib13","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.freeradbiomed.2013.01.023","article-title":"Xanthine oxidoreductase is a critical mediator of cigarette smoke-induced endothelial cell DNA damage and apoptosis","volume":"60","author":"Kim","year":"2013","journal-title":"Free Radic Biol Med"},{"issue":"6","key":"10.1016\/j.chpulm.2025.100212_bib14","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0180455","article-title":"Contribution of reactive oxygen species to the pathogenesis of pulmonary arterial hypertension","volume":"12","author":"Jernigan","year":"2017","journal-title":"PLoS One"},{"issue":"5","key":"10.1016\/j.chpulm.2025.100212_bib15","article-title":"Oxidative profiling of the failing right heart in rats with pulmonary hypertension","volume":"12","author":"Wang","year":"2017","journal-title":"PLoS One"},{"issue":"23","key":"10.1016\/j.chpulm.2025.100212_bib16","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.121.022712","article-title":"Increased lung uric acid deteriorates pulmonary arterial hypertension","volume":"10","author":"Watanabe","year":"2021","journal-title":"J Am Heart Assoc"},{"key":"10.1016\/j.chpulm.2025.100212_bib17","doi-asserted-by":"crossref","DOI":"10.1016\/j.pupt.2022.102166","article-title":"Allopurinol treatment reduced vascular remodeling and improved vascular functions in monocrotaline-induced pulmonary hypertensive rats","volume":"77","author":"Gokcen","year":"2022","journal-title":"Pulm Pharmacol Ther"},{"issue":"5","key":"10.1016\/j.chpulm.2025.100212_bib18","doi-asserted-by":"crossref","first-page":"L617","DOI":"10.1152\/ajplung.00177.2023","article-title":"Kynurenine pathway metabolism evolves with development of preclinical and scleroderma-associated pulmonary arterial hypertension","volume":"325","author":"Simpson","year":"2023","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib19","doi-asserted-by":"crossref","first-page":"L54","DOI":"10.1152\/ajplung.00057.2024","article-title":"Aberrant long-chain fatty acid metabolism associated with evolving systemic sclerosis-associated pulmonary arterial hypertension","volume":"327","author":"Coursen","year":"2024","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"11","key":"10.1016\/j.chpulm.2025.100212_bib20","doi-asserted-by":"crossref","first-page":"2737","DOI":"10.1002\/art.38098","article-title":"2013 classification criteria for systemic sclerosis: An American College of Rheumatology\/European League Against Rheumatism Collaborative Initiative","volume":"65","author":"Van Den Hoogen","year":"2013","journal-title":"Arthritis Rheum"},{"issue":"4","key":"10.1016\/j.chpulm.2025.100212_bib21","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1183\/13993003.01032-2015","article-title":"2015 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"46","author":"Gali\u00e8","year":"2015","journal-title":"Eur Respir J"},{"key":"10.1016\/j.chpulm.2025.100212_bib22","doi-asserted-by":"crossref","first-page":"2290","DOI":"10.1152\/ajpheart.00515.2003","article-title":"Vascular signaling by free radicals role of xanthine oxidoreductase and NAD(P)H oxidase in endothelial superoxide production in response to oscillatory shear stress","volume":"285","author":"Scott McNally","year":"2003","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"10.1016\/j.chpulm.2025.100212_bib23","article-title":"Clinical features of pulmonary arterial hypertension associated with systemic sclerosis","volume":"10","author":"Tuhy","year":"2023","journal-title":"Front Med (Lausanne)"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib24","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1183\/13993003.00879-2022","article-title":"2022 ESC\/ERS guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"61","author":"Humbert","year":"2023","journal-title":"Eur Respir J"},{"key":"10.1016\/j.chpulm.2025.100212_bib25","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur Respir J"},{"issue":"4","key":"10.1016\/j.chpulm.2025.100212_bib26","doi-asserted-by":"crossref","first-page":"1299","DOI":"10.1152\/jappl.2001.90.4.1299","article-title":"Generation of oxidative stress contributes to the development of pulmonary hypertension induced by hypoxia","volume":"90","author":"Hoshikawa","year":"2001","journal-title":"J Appl Physiol"},{"issue":"2","key":"10.1016\/j.chpulm.2025.100212_bib27","doi-asserted-by":"crossref","first-page":"L233","DOI":"10.1152\/ajplung.00166.2007","article-title":"Contribution of xanthine oxidase-derived superoxide to chronic hypoxic pulmonary hypertension in neonatal rats","volume":"294","author":"Jankov","year":"2008","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"11","key":"10.1016\/j.chpulm.2025.100212_bib28","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0027531","article-title":"Xanthine oxidase-derived ROS upregulate Egr-1 via ERK1\/2 in PA smooth muscle cells; model to test impact of extracellular ROS in chronic hypoxia","volume":"6","author":"Hartney","year":"2011","journal-title":"PLoS One"},{"issue":"4","key":"10.1016\/j.chpulm.2025.100212_bib29","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1378\/chest.11-1267","article-title":"Independent association of urinary F2-isoprostanes with survival in pulmonary arterial hypertension","volume":"142","author":"Cracowski","year":"2012","journal-title":"Chest"},{"issue":"2","key":"10.1016\/j.chpulm.2025.100212_bib30","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jacc.2015.10.072","article-title":"Metabolic profiling of right ventricular-pulmonary vascular function reveals circulating biomarkers of pulmonary hypertension","volume":"67","author":"Lewis","year":"2016","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib31","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jjcc.2020.12.013","article-title":"Uric acid and cardiovascular disease: a clinical review","volume":"78","author":"Saito","year":"2021","journal-title":"J Cardiol"},{"issue":"10359","key":"10.1016\/j.chpulm.2025.100212_bib32","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1016\/S0140-6736(22)01657-9","article-title":"Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial","volume":"400","author":"Mackenzie","year":"2022","journal-title":"Lancet"},{"issue":"22","key":"10.1016\/j.chpulm.2025.100212_bib33","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1093\/eurheartj\/ehz119","article-title":"Febuxostat for cerebral and CaRdiorenovascular Events PrEvEntion StuDy","volume":"40","author":"Kojima","year":"2019","journal-title":"Eur Heart J"},{"issue":"13","key":"10.1016\/j.chpulm.2025.100212_bib34","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1056\/NEJMoa1710895","article-title":"Cardiovascular safety of febuxostat or allopurinol in patients with gout","volume":"378","author":"White","year":"2018","journal-title":"N Engl J Med"},{"issue":"19","key":"10.1016\/j.chpulm.2025.100212_bib35","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.122.026301","article-title":"Lowering uric acid may improve prognosis in patients with hyperuricemia and heart failure with preserved ejection fraction","volume":"11","author":"Nishino","year":"2022","journal-title":"J Am Heart Assoc"},{"issue":"20","key":"10.1016\/j.chpulm.2025.100212_bib36","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1161\/CIRCULATIONAHA.114.014536","article-title":"Effects of xanthine oxidase inhibition in hyperuricemic heart failure patients: the xanthine oxidase inhibition for hyperuricemic heart failure patients (EXACT-HF) study","volume":"131","author":"Givertz","year":"2015","journal-title":"Circulation"},{"key":"10.1016\/j.chpulm.2025.100212_bib37","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.2147\/COPD.S260917","article-title":"Allopurinol in patients with pulmonary hypertension associated with chronic lung disease","volume":"15","author":"Liu Shiu Cheong","year":"2020","journal-title":"Int J COPD"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib38","article-title":"Effects of uric acid on ischemic diseases, stratified by lipid levels: a drug-target, nonlinear Mendelian randomization study","volume":"14","author":"Kim","year":"2024","journal-title":"Sci Rep"},{"issue":"20","key":"10.1016\/j.chpulm.2025.100212_bib39","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.123.030625","article-title":"Uric acid levels, number of standard modifiable cardiovascular risk factors, and prognosis in patients with coronary artery disease: a large cohort study in Asia","volume":"12","author":"Cui","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"5","key":"10.1016\/j.chpulm.2025.100212_bib40","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s40292-023-00602-4","article-title":"The results of the URRAH (Uric Acid Right for Heart Health) project: a focus on hyperuricemia in relation to cardiovascular and kidney disease and its role in metabolic dysregulation","volume":"30","author":"Maloberti","year":"2023","journal-title":"High Blood Press Cardiovasc Prev"},{"issue":"1","key":"10.1016\/j.chpulm.2025.100212_bib41","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1183\/09031936.00013309","article-title":"Increased xanthine oxidase activity in idiopathic pulmonary arterial hypertension","volume":"34","author":"Spiekermann","year":"2009","journal-title":"Eur Respir J"}],"container-title":["CHEST Pulmonary"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2949789225000790?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2949789225000790?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T02:35:27Z","timestamp":1774060527000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2949789225000790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["S2949789225000790"],"URL":"https:\/\/doi.org\/10.1016\/j.chpulm.2025.100212","relation":{},"ISSN":["2949-7892"],"issn-type":[{"value":"2949-7892","type":"print"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Increased Xanthine Oxidoreductase Activity in Patients With Systemic Sclerosis-Associated Pulmonary Arterial Hypertension","name":"articletitle","label":"Article Title"},{"value":"CHEST Pulmonary","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.chpulm.2025.100212","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc under license from the American College of Chest Physicians.","name":"copyright","label":"Copyright"}],"article-number":"100212"}}