{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:59:08Z","timestamp":1790841548715,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/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\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08HL166950"],"award-info":[{"award-number":["K08HL166950"]}],"id":[{"id":"10.13039\/100000002","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>Methamphetamine\u2010associated pulmonary arterial hypertension (Meth\u2010APAH) is an increasingly recognized cause of pulmonary arterial hypertension (PAH) and is associated with worse outcomes than idiopathic PAH (IPAH). Although both share histopathologic features of pulmonary vascular remodeling, the molecular basis for their clinical divergence remains unclear, particularly at the metabolic level. We performed high\u2010throughput, non\u2010targeted plasma metabolomic profiling in patients with Meth\u2010APAH and matched IPAH controls enrolled from the Pulmonary Arterial Hypertension Biobank. Multivariate and regression analyses adjusted for demographics, hemodynamic severity, and PAH therapies were used to identify distinguishing metabolites. Among 98 patients (49 Meth\u2010APAH and 49 IPAH), baseline hemodynamics and functional status were similar, although Meth\u2010APAH patients had higher smoking prevalence and lower PAH therapy use. Of 757 metabolites passing quality control, 55 differed significantly between subtypes, including 22 enriched in Meth\u2010APAH. Meth\u2010APAH was characterized by elevations in amino acid\u2013derived metabolites and pro\u2010inflammatory eicosanoids, implicating dysregulation of the kynurenine pathway and arachidonic acid metabolism. IPAH demonstrated relative enrichment of branched\u2010chain amino acids, antioxidant metabolites, and specialized pro\u2010resolving mediators. Exploratory survival analyses identified associations between subtype\u2010discriminating metabolites and outcomes. These findings reveal metabolic heterogeneity across PAH etiologies and support biologically distinct pathobiology in Meth\u2010APAH and IPAH.<\/jats:p>","DOI":"10.1002\/pul2.70361","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T11:32:26Z","timestamp":1784115146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Divergent Inflammatory and Bioenergetic Metabolomic Signatures Distinguish Methamphetamine\u2010Associated From Idiopathic Pulmonary Arterial Hypertension"],"prefix":"10.1002","volume":"16","author":[{"given":"Hannah K.","family":"Robertson","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Yuguchi","sequence":"additional","affiliation":[{"name":"UC San Diego Health La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Gurholt","sequence":"additional","affiliation":[{"name":"UC San Diego Health La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Cincinnati Children's Hospital Medical Center Cincinnati Ohio USA"},{"name":"Cincinnati College of Medicine Cincinnati Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nick H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine University of California San Diego La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine University of California San Diego La Jolla California 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