{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T11:35:27Z","timestamp":1794483327235,"version":"4.9.1"},"reference-count":48,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:00:00Z","timestamp":1793491200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82500078"],"award-info":[{"award-number":["82500078"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8247023090"],"award-info":[{"award-number":["8247023090"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017357","name":"Science and Technology Projects of Fujian Province","doi-asserted-by":"publisher","award":["2024Y96010029"],"award-info":[{"award-number":["2024Y96010029"]}],"id":[{"id":"10.13039\/100017357","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011635","name":"Fuwai Hospital, Chinese Academy of Medical Sciences","doi-asserted-by":"publisher","award":["NCRCSZ-2025-009"],"award-info":[{"award-number":["NCRCSZ-2025-009"]}],"id":[{"id":"10.13039\/501100011635","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["iScience"],"published-print":{"date-parts":[[2026,11]]},"DOI":"10.1016\/j.isci.2026.117792","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:21:21Z","timestamp":1791400881000},"page":"117792","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma proteomic analysis identified potential therapeutic targets for pulmonary arterial hypertension"],"prefix":"10.1016","volume":"29","author":[{"given":"Song","family":"Hu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqi","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang-Shan","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Ting","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengsong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhennan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5687-9830","authenticated-orcid":false,"given":"Lu","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.isci.2026.117792_bib1","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1093\/eurheartj\/ehac237","article-title":"2022 ESC\/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension","volume":"43","author":"Humbert","year":"2022","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.isci.2026.117792_bib2","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1161\/CIRCULATIONAHA.123.067005","article-title":"ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension","volume":"150","author":"Bian","year":"2024","journal-title":"Circulation"},{"key":"10.1016\/j.isci.2026.117792_bib3","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41576-020-0268-2","article-title":"Genetics meets proteomics: perspectives for large population-based studies","volume":"22","author":"Suhre","year":"2021","journal-title":"Nat. Rev. Genet."},{"key":"10.1016\/j.isci.2026.117792_bib4","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/S2213-2600(17)30161-3","article-title":"Plasma proteome analysis in patients with pulmonary arterial hypertension: an observational cohort study","volume":"5","author":"Rhodes","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"10.1016\/j.isci.2026.117792_bib5","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1164\/rccm.202105-1118OC","article-title":"Using the Plasma Proteome for Risk Stratifying Patients with Pulmonary Arterial Hypertension","volume":"205","author":"Rhodes","year":"2022","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.isci.2026.117792_bib6","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1038\/s41586-023-06563-x","article-title":"Large-scale plasma proteomics comparisons through genetics and disease associations","volume":"622","author":"Eldjarn","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.isci.2026.117792_bib7","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.tig.2022.08.005","article-title":"Insights from multi-omics integration in complex disease primary tissues","volume":"39","author":"Kreitmaier","year":"2023","journal-title":"Trends Genet."},{"key":"10.1016\/j.isci.2026.117792_bib8","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1093\/hmg\/dds073","article-title":"BMPR-II deficiency elicits pro-proliferative and anti-apoptotic responses through the activation of TGFbeta-TAK1-MAPK pathways in PAH","volume":"21","author":"Nasim","year":"2012","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.isci.2026.117792_bib9","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1016\/j.hlc.2022.02.007","article-title":"Immune Cells in Pulmonary Arterial Hypertension","volume":"31","author":"Ni","year":"2022","journal-title":"Heart Lung Circ."},{"key":"10.1016\/j.isci.2026.117792_bib10","doi-asserted-by":"crossref","DOI":"10.1080\/10641963.2025.2486829","article-title":"Cinnamaldehyde alleviates pulmonary hypertension by affecting vascular remodeling through the TLR4\/NF-kB\/HIF-1a pathway","volume":"47","author":"Zhang","year":"2025","journal-title":"Clin. Exp. Hypertens."},{"key":"10.1016\/j.isci.2026.117792_bib11","doi-asserted-by":"crossref","DOI":"10.3389\/fcell.2025.1690124","article-title":"Targeting endothelial cells: the pathological mechanisms and therapeutic innovations in pulmonary arterial hypertension","volume":"13","author":"Fan","year":"2025","journal-title":"Front. Cell Dev. Biol."},{"key":"10.1016\/j.isci.2026.117792_bib12","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aag1166","article-title":"The druggable genome and support for target identification and validation in drug development","volume":"9","author":"Finan","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.isci.2026.117792_bib13","doi-asserted-by":"crossref","DOI":"10.1161\/ATVBAHA.125.323681","article-title":"Activin A-Endothelin-1 Axis Governs Pulmonary Vascular Remodeling: Mechanistic Basis for Emerging Therapies in PAH","volume":"46","author":"Faizah","year":"2026","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.isci.2026.117792_bib14","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nrcardio.2011.87","article-title":"Mechanisms of disease: pulmonary arterial hypertension","volume":"8","author":"Schermuly","year":"2011","journal-title":"Nat. Rev. Cardiol."},{"key":"10.1016\/j.isci.2026.117792_bib15","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.1042\/CS20190835","article-title":"Notch3 signalling and vascular remodelling in pulmonary arterial hypertension","volume":"133","author":"Morris","year":"2019","journal-title":"Clin. Sci."},{"key":"10.1016\/j.isci.2026.117792_bib16","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1038\/nm.2021","article-title":"Notch3 signaling promotes the development of pulmonary arterial hypertension","volume":"15","author":"Li","year":"2009","journal-title":"Nat. Med."},{"key":"10.1016\/j.isci.2026.117792_bib17","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3109\/01902148.2015.1060545","article-title":"Inhibition of Notch3 prevents monocrotaline-induced pulmonary arterial hypertension","volume":"41","author":"Zhang","year":"2015","journal-title":"Exp. Lung Res."},{"key":"10.1016\/j.isci.2026.117792_bib18","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abl5471","article-title":"JAGGED-NOTCH3 signaling in vascular remodeling in pulmonary arterial hypertension","volume":"14","author":"Zhang","year":"2022","journal-title":"Sci. Transl. Med."},{"key":"10.1016\/j.isci.2026.117792_bib19","doi-asserted-by":"crossref","first-page":"F212","DOI":"10.1152\/ajprenal.00146.2022","article-title":"The kidney protects against sepsis by producing systemic uromodulin","volume":"323","author":"LaFavers","year":"2022","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"10.1016\/j.isci.2026.117792_bib20","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1093\/ndt\/gfz008","article-title":"Association of serum uromodulin with mortality and cardiovascular disease in the elderly-the Cardiovascular Health Study","volume":"35","author":"Steubl","year":"2020","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.isci.2026.117792_bib21","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1093\/cvr\/cvaa081","article-title":"Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signalling","volume":"117","author":"Alesutan","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"10.1016\/j.isci.2026.117792_bib22","article-title":"The role of uromodulin in cardiovascular disease: a review","volume":"11","author":"Chen","year":"2024","journal-title":"Front. Cardiovasc. Med."},{"key":"10.1016\/j.isci.2026.117792_bib23","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1164\/rccm.201512-2380OC","article-title":"Role for Runt-related Transcription Factor 2 in Proliferative and Calcified Vascular Lesions in Pulmonary Arterial Hypertension","volume":"194","author":"Ruffenach","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.isci.2026.117792_bib24","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1164\/rccm.201806-1027LE","article-title":"Enhanced Pulmonary Artery Radiodensity in Pulmonary Arterial Hypertension: A Sign of Early Calcification?","volume":"199","author":"Tanguay","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.isci.2026.117792_bib25","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.vph.2014.10.002","article-title":"The role of the osteoprotegerin\/tumor necrosis factor related apoptosis-inducing ligand axis in the pathogenesis of pulmonary arterial hypertension","volume":"63","author":"Lawrie","year":"2014","journal-title":"Vasc. Pharmacol."},{"key":"10.1016\/j.isci.2026.117792_bib26","doi-asserted-by":"crossref","DOI":"10.3390\/ijms24076725","article-title":"The Prognostic, Diagnostic, and Therapeutic Potential of TRAIL Signalling in Cardiovascular Diseases","volume":"24","author":"Kelland","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.isci.2026.117792_bib27","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.add5028","article-title":"Breast tumors interfere with endothelial TRAIL at the premetastatic niche to promote cancer cell seeding","volume":"9","author":"Riera-Domingo","year":"2023","journal-title":"Sci. Adv."},{"key":"10.1016\/j.isci.2026.117792_bib28","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.bcp.2007.10.020","article-title":"Expression, regulation and function of trail in atherosclerosis","volume":"75","author":"Kavurma","year":"2008","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.isci.2026.117792_bib29","doi-asserted-by":"crossref","first-page":"2250","DOI":"10.1161\/01.CIR.0000062702.60708.C4","article-title":"TRAIL promotes the survival and proliferation of primary human vascular endothelial cells by activating the Akt and ERK pathways","volume":"107","author":"Secchiero","year":"2003","journal-title":"Circulation"},{"key":"10.1016\/j.isci.2026.117792_bib30","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1007\/s00018-004-4197-6","article-title":"TRAIL promotes the survival, migration and proliferation of vascular smooth muscle cells","volume":"61","author":"Secchiero","year":"2004","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.isci.2026.117792_bib31","doi-asserted-by":"crossref","first-page":"7754","DOI":"10.1074\/jbc.M706927200","article-title":"TRAIL stimulates proliferation of vascular smooth muscle cells via activation of NF-kappaB and induction of insulin-like growth factor-1 receptor","volume":"283","author":"Kavurma","year":"2008","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.isci.2026.117792_bib32","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1084\/jem.20112716","article-title":"Inhibition of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) reverses experimental pulmonary hypertension","volume":"209","author":"Hameed","year":"2012","journal-title":"J. Exp. Med."},{"key":"10.1016\/j.isci.2026.117792_bib33","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2017.423","article-title":"Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells","volume":"8","author":"Shlyakhtina","year":"2017","journal-title":"Cell Death Dis."},{"key":"10.1016\/j.isci.2026.117792_bib34","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2025.1549808","article-title":"Advances in the study of death receptor 5","volume":"16","author":"Qiao","year":"2025","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.isci.2026.117792_bib35","first-page":"613","article-title":"The Dual Role of the TRAIL-DR5 Signaling Axis in Cardiovascular Disease: From Molecular Mechanisms to Targeted Therapies","volume":"19","author":"Cao","year":"2025","journal-title":"Biologics"},{"key":"10.1016\/j.isci.2026.117792_bib36","doi-asserted-by":"crossref","first-page":"L1115","DOI":"10.1152\/ajplung.00476.2019","article-title":"The hallmarks of severe pulmonary arterial hypertension: the cancer hypothesis-ten years later","volume":"318","author":"Cool","year":"2020","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"10.1016\/j.isci.2026.117792_bib37","doi-asserted-by":"crossref","first-page":"621","DOI":"10.7150\/thno.72297","article-title":"FAM3C in circulating tumor-derived extracellular vesicles promotes non-small cell lung cancer growth in secondary sites","volume":"13","author":"Thuya","year":"2023","journal-title":"Theranostics"},{"key":"10.1016\/j.isci.2026.117792_bib38","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.00436-2025","article-title":"A cautionary note on the naive use of general-population biobanks to study pulmonary arterial hypertension, with a focus on Mendelian randomisation","volume":"66","author":"Woolf","year":"2025","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.isci.2026.117792_bib39","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1161\/CIRCRESAHA.121.319971","article-title":"The Latest in Animal Models of Pulmonary Hypertension and Right Ventricular Failure","volume":"130","author":"Boucherat","year":"2022","journal-title":"Circ. Res."},{"key":"10.1016\/j.isci.2026.117792_bib40","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.ijcard.2012.10.026","article-title":"Elderly patients diagnosed with idiopathic pulmonary arterial hypertension: results from the COMPERA registry","volume":"168","author":"Hoeper","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"10.1016\/j.isci.2026.117792_bib41","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1164\/rccm.201203-0383OC","article-title":"Changing demographics, epidemiology, and survival of incident pulmonary arterial hypertension: results from the pulmonary hypertension registry of the United Kingdom and Ireland","volume":"186","author":"Ling","year":"2012","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"10.1016\/j.isci.2026.117792_bib42","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1093\/eurheartj\/ehx254","article-title":"UK Biobank: opportunities for cardiovascular research","volume":"40","author":"Littlejohns","year":"2019","journal-title":"Eur. Heart J."},{"key":"10.1016\/j.isci.2026.117792_bib43","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","article-title":"Plasma proteomic associations with genetics and health in the UK Biobank","volume":"622","author":"Sun","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.isci.2026.117792_bib44","doi-asserted-by":"crossref","first-page":"3292","DOI":"10.1038\/s41596-024-01020-z","article-title":"Using clusterProfiler to characterize multiomics data","volume":"19","author":"Xu","year":"2024","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.isci.2026.117792_bib45","doi-asserted-by":"crossref","first-page":"1540","DOI":"10.1038\/s41590-023-01588-w","article-title":"Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets","volume":"24","author":"Zhao","year":"2023","journal-title":"Nat. Immunol."},{"key":"10.1016\/j.isci.2026.117792_bib46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S2213-2600(18)30409-0","article-title":"Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis","volume":"7","author":"Rhodes","year":"2019","journal-title":"Lancet Respir. Med."},{"key":"10.1016\/j.isci.2026.117792_bib47","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1001\/jamapsychiatry.2021.0005","article-title":"Association of Antihypertensive Drug Target Genes With Psychiatric Disorders: A Mendelian Randomization Study","volume":"78","author":"Chauquet","year":"2021","journal-title":"JAMA Psychiatry"},{"key":"10.1016\/j.isci.2026.117792_bib48","doi-asserted-by":"crossref","first-page":"4391","DOI":"10.1002\/sim.7501","article-title":"Practical recommendations for reporting Fine-Gray model analyses for competing risk data","volume":"36","author":"Austin","year":"2017","journal-title":"Stat. Med."}],"container-title":["iScience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226031731?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2589004226031731?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T10:36:50Z","timestamp":1794479810000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2589004226031731"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,11]]},"references-count":48,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,11]]}},"alternative-id":["S2589004226031731"],"URL":"https:\/\/doi.org\/10.1016\/j.isci.2026.117792","relation":{},"ISSN":["2589-0042"],"issn-type":[{"value":"2589-0042","type":"print"}],"subject":[],"published":{"date-parts":[[2026,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Plasma proteomic analysis identified potential therapeutic targets for pulmonary arterial hypertension","name":"articletitle","label":"Article Title"},{"value":"iScience","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.isci.2026.117792","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"117792"}}