{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:04:10Z","timestamp":1789621450632,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82607079"],"award-info":[{"award-number":["82607079"]}],"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":["82470318"],"award-info":[{"award-number":["82470318"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Current biomarkers for idiopathic pulmonary arterial hypertension (IPAH) lack disease specificity and provide limited biological insight. We hypothesized that integrating population\u2010based proteomics with genetic evidence would identify robust IPAH\u2010associated proteins relevant to risk stratification, early detection, prognosis, sex differences, and candidate drug\u2010repurposing opportunities.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 2,918 plasma proteins in 44,137 predominantly European\u2010ancestry UK Biobank participants aged 40\u201369 years, including 252 incident and 141 prevalent IPAH cases. Proteins associated with IPAH were identified using Cox and logistic regression analyses, prioritized by cis\u2010Mendelian randomization, and assessed through cross\u2010ancestry effect\u2010direction concordance and sensitivity analyses. Unsupervised clustering, nested cross\u2010validated prediction models, and target\u2013drug annotation were used for downstream evaluation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighteen proteins showed convergent epidemiological and genetic evidence, and 12 remained supported in cross\u2010ancestry and sensitivity analyses. These proteins defined a high\u2010mortality endotype characterized by vascular and ventricular remodeling. Combined clinical and proteomic models achieved AUCs of 0.779 for incident IPAH and 0.768 for mortality. Proteomic contributions differed by sex, and target\u2013drug annotation identified six drug\u2010linked proteins, highlighting ANXA2\u2010linked\n                      <jats:italic>Artenimol<\/jats:italic>\n                      as a repurposing candidate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Twelve biologically plausible IPAH\u2010associated proteins inform risk stratification, prediction, sex\u2010related characterization, and therapeutic prioritization. Independent multi\u2010ancestry validation and mechanistic studies are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/advs.77687","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:36:48Z","timestamp":1789619808000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proteogenomic Profiling of Idiopathic Pulmonary Arterial Hypertension Identifies Sex\u2010Differential Proteins and Candidate Therapeutic Targets"],"prefix":"10.1002","author":[{"given":"Xinjie","family":"Lin","sequence":"first","affiliation":[{"name":"Pediatric Cardiac Surgery Center State Key Laboratory of Cardiovascular Disease National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for Cardiovascular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yangchang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology The First Affiliated Hospital of Chongqing University of Chinese Medicine  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Pu","sequence":"additional","affiliation":[{"name":"School of General Education Chongqing College of Traditional Chinese Medicine  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duanke","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Ophthalmology Beijing Tongren Eye Center Beijing Tongren Hospital Beijing Key Laboratory of Intelligent Diagnosis Technology and Equipment for Optic Nerve\u2010Related Eye Diseases, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Lei","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery Center State Key Laboratory of Cardiovascular Disease National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for Cardiovascular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Ma","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery Center State Key Laboratory of Cardiovascular Disease National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for Cardiovascular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyu","family":"He","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery Center State Key Laboratory of Cardiovascular Disease National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for Cardiovascular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Dou","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery Center State Key Laboratory of Cardiovascular Disease National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for Cardiovascular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuze","family":"Liu","sequence":"additional","affiliation":[{"name":"Pediatric Cardiac Surgery Center State Key Laboratory of Cardiovascular Disease National Clinical Research Center for Cardiovascular Diseases Fuwai Hospital, Chinese Academy of Medical Sciences &amp; Peking Union Medical College\/National Center for Cardiovascular Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dengyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinge","family":"He","sequence":"additional","affiliation":[{"name":"Zhengzhou No. 7 People's Hospital  Zhengzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshang","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Psychiatry Faculty of Brain Science University College London  London 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