{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T07:03:23Z","timestamp":1788851003458,"version":"build-2803163510"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2013,9,17]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>The pathogenic mechanisms underlying pulmonary arterial hypertension resulting from schistosomiasis, one of the most common causes of pulmonary hypertension worldwide, remain unknown. We hypothesized that transforming growth factor-\u03b2 (TGF-\u03b2) signaling as a consequence of Th2 inflammation is critical for the pathogenesis of this disease.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Mice sensitized and subsequently challenged with\n              <jats:italic>Schistosoma mansoni<\/jats:italic>\n              eggs developed pulmonary hypertension associated with an increase in right ventricular systolic pressure, thickening of the pulmonary artery media, and right ventricular hypertrophy. Rho-kinase\u2013dependent vasoconstriction accounted for \u224860% of the increase in right ventricular systolic pressure. The pulmonary vascular remodeling and pulmonary hypertension were dependent on increased TGF-\u03b2 signaling, as pharmacological blockade of the TGF-\u03b2 ligand and receptor, and mice lacking Smad3 were significantly protected from\n              <jats:italic>Schistosoma<\/jats:italic>\n              -induced pulmonary hypertension. Blockade of TGF-\u03b2 signaling also led to a decrease in interleukin-4 and interleukin-13 concentrations, which drive the Th2 responses characteristic of schistosomiasis lung pathology. Lungs of patients with schistosomiasis-associated pulmonary arterial hypertension have evidence of TGF-\u03b2 signaling in their remodeled pulmonary arteries.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion\u2014<\/jats:title>\n            <jats:p>\n              Experimental\n              <jats:italic>S mansoni<\/jats:italic>\n              \u2013induced pulmonary vascular disease relies on canonical TGF-\u03b2 signaling.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.113.003072","type":"journal-article","created":{"date-parts":[[2013,8,20]],"date-time":"2013-08-20T05:02:57Z","timestamp":1376974977000},"page":"1354-1364","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":93,"title":["Transforming Growth Factor-\u03b2 Signaling Promotes Pulmonary Hypertension Caused by\n            <i>Schistosoma Mansoni<\/i>"],"prefix":"10.1161","volume":"128","author":[{"given":"Brian B.","family":"Graham","sequence":"first","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Chabon","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Gebreab","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Poole","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Debella","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Davis","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Sanders","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. 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Jose Hospital, Universidade de Pernambuco in Recife, Recife, Brazil (A.B.); Division of Cardiology, University of Pittsburgh, Pittsburgh, PA (H.C.C.); School of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghazwan","family":"Butrous","sequence":"additional","affiliation":[{"name":"From the Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine (B.B.G., J.C., L.G., J.P., E.D., L.D., T.T., L.S., N.D., R.W.V.) and Department of Pathology (X.-J.W.), Anschutz Medical Campus, Aurora, CO; Pulmonary Vascular Research Institute (B.B.G., A.B., H.C.C., G.B., R.M.T.); Memorial S. 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