{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T05:01:22Z","timestamp":1790312482603,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,6,18]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Pulmonary arterial hypertension (PAH) ultimately leads to right ventricular failure and premature death. The identification of circulating biomarkers with prognostic utility is considered a priority. As chronic inflammation is recognized as key pathogenic driver, we sought to identify inflammation\u2010related circulating proteins that add incremental value to current risk stratification models for long\u2010term survival in patients with PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Plasma levels of 384 inflammatory proteins were measured with the proximity extension assay technology in patients with PAH (n=60) and controls with normal hemodynamics (n=28). Among these, 51 analytes were significantly overexpressed in the plasma of patients with PAH compared with controls. Cox proportional hazard analyses and C\u2010statistics were performed to assess the prognostic value and the incremental prognostic value of differentially expressed proteins. A panel of 6 proteins (CRIM1 [cysteine rich transmembrane bone morphogenetic protein regulator 1], HGF [hepatocyte growth factor], FSTL3 [follistatin\u2010like 3], PLAUR [plasminogen activator, urokinase receptor], CLSTN2 [calsyntenin 2], SPON1 [spondin 1]) were independently associated with death\/lung transplantation at the time of PAH diagnosis after adjustment for the 2015 European Society of Cardiology\/European Respiratory Society guidelines, the REVEAL (Registry to Evaluate Early and Long\u2010Term PAH Disease Management) 2.0 risk scores, and the refined 4\u2010strata risk assessment. CRIM1, PLAUR, FSTL3, and SPON1 showed incremental prognostic value on top of the predictive models. As determined by Western blot, FSTL3 and SPON1 were significantly upregulated in the right ventricle of patients with PAH and animal models (monocrotaline\u2010injected and pulmonary artery banding\u2010subjected rats).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In addition to revealing new actors likely involved in cardiopulmonary remodeling in PAH, our screening identified promising circulating biomarkers to improve risk prediction in PAH, which should be externally confirmed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.123.032888","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T07:09:52Z","timestamp":1718348992000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Prognostic Significance of Proteomics\u2010Discovered Circulating Inflammatory Biomarkers in Patients With Pulmonary Arterial Hypertension"],"prefix":"10.1161","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8197-3274","authenticated-orcid":false,"given":"Tetsuro","family":"Yokokawa","sequence":"first","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec","place":["Qu\u00e9bec City, Canada"]},{"name":"Fukushima Medical University","place":["Fukushima, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-7488","authenticated-orcid":false,"given":"Olivier","family":"Boucherat","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec","place":["Qu\u00e9bec City, Canada"]},{"name":"Universit\u00e9 Laval","place":["Qu\u00e9bec City, 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