{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:07:52Z","timestamp":1790647672640,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"16","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,8,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Activation of the plasma kynurenine pathway (KP) may contribute to the progression of pulmonary arterial hypertension (PAH). We investigated the functional role and molecular mechanisms of KP activation in PAH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">KP activity was measured in the lungs and plasma of humans and rodents with pulmonary hypertension (PH). KP activity was modulated in lung microvascular endothelial cells in\u00a0vitro, and through daily oral administration of epacadostat, an inhibitor of IDO\u20101 (indoleamine 2,3\u2010dioxygenase), the rate\u2010limiting enzyme of the KP, in rats with monocrotaline\u2010induced PH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              IDO\u20101 expression was increased in peripheral blood mononuclear cells but not in lung tissue of patients with PAH and in rats with monocrotaline\u2010induced PH. Epacadostat prevented KP activation and the development of monocrotaline\u2010induced PH, significantly reduced right ventricular systolic pressure (58\u00b19 versus 42\u00b14 and 46\u00b16\u2009mm\u2009Hg for placebo versus epacadostat 50 and 100\u2009mg\/kg, respectively,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.001), pulmonary arterial remodeling (wall thickness, 64\u00b13 versus 58\u00b13 and 58\u00b13%,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.001), perivascular inflammation, and right ventricular remodeling (Fulton index, 0.49\u00b10.05 versus 0.36\u00b10.06 and 0.39\u00b10.04,\n              <jats:italic toggle=\"no\">P<\/jats:italic>\n              &lt;0.001). IDO\u20101 overexpression contributed to KP activation and de novo nicotinamide adenine dinucleotide\n              <jats:sup>+<\/jats:sup>\n              synthesis, increased mitochondrial membrane potential, and endothelial cell proliferation. Inhibition of IDO\u20101 using siRNA or epacadostat reversed these effects and inhibited the inflammatory response.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Increased IDO\u20101 expression in peripheral blood mononuclear cells may drive KP activation and promote pulmonary vascular remodeling in PAH. Epacadostat prevents the development of monocrotaline\u2010induced PH. These findings suggest a novel approach for the treatment of PAH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.040896","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T11:29:17Z","timestamp":1754998157000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["IDO\u20101 Promotes Pulmonary Vascular Remodeling Via Kynurenine Pathway in Pulmonary Arterial Hypertension"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4898-1907","authenticated-orcid":false,"given":"Zongye","family":"Cai","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]},{"name":"Erasmus MC, University Medical Center","place":["Rotterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ly","family":"Tu","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, Hypertension Pulmonaire : Pathophysiologie et Innovation Th\u00e9rapeutique (HPPIT)","place":["Le Kremlin\u2010Bic\u00eatre, France"]},{"name":"Universit\u00e9 Paris\u2010Saclay, School of Medicine, HPPIT","place":["Le Kremlin\u2010Bic\u00eatre, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-9525","authenticated-orcid":false,"given":"Siyu","family":"Tian","sequence":"additional","affiliation":[{"name":"Erasmus MC, University Medical Center","place":["Rotterdam, The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8322-133X","authenticated-orcid":false,"given":"Lin","family":"Deng","sequence":"additional","affiliation":[{"name":"The Eighth Affiliated Hospital of Sun Yat\u2010sen University","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahong","family":"Fu","sequence":"additional","affiliation":[{"name":"The Second Affiliated Hospital, Zhejiang University School of Medicine","place":["Hangzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carole","family":"Phan","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 999, Hypertension Pulmonaire : Pathophysiologie et Innovation Th\u00e9rapeutique (HPPIT)","place":["Le Kremlin\u2010Bic\u00eatre, France"]},{"name":"Universit\u00e9 Paris\u2010Saclay, School of Medicine, HPPIT","place":["Le Kremlin\u2010Bic\u00eatre, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7223-4565","authenticated-orcid":false,"given":"Thierry P. 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