{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:45:59Z","timestamp":1787013959408,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2018,9,16]],"date-time":"2018-09-16T00:00:00Z","timestamp":1537056000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007150","name":"United Therapeutics Corporation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007150","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Pulmonary arterial hypertension (PAH) is a life\u2010threatening disease that leads to progressive pulmonary hypertension, right heart failure and death. Parenteral prostaglandins (PGs), including treprostinil, a prostacyclin analogue, represent the most effective medical treatment for severe PAH. We investigated the effect of treprostinil on established severe PAH and underlying mechanisms using the rat SU5416 (SU, a VEGF receptor\u20102 inhibitor)\u2010chronic hypoxia (Hx) model of PAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      Male Sprague Dawley rats were injected with SU (20\u00a0mg\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      , s.c.) followed by 3\u00a0weeks of Hx (10% O\n                      <jats:sub>2<\/jats:sub>\n                      ) to induce severe PAH. Four weeks post\u2010SU injection, baseline right ventricular (RV) systolic pressure (RVSP) was measured, and the rats were randomized to receive vehicle or treprostinil treatment (Trep\u2010100: 100\u00a0ng\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      or Trep\u2010810: 810\u00a0ng\u00b7kg\n                      <jats:sup>\u22121<\/jats:sup>\n                      \u00b7min\n                      <jats:sup>\u22121<\/jats:sup>\n                      ). Following 3\u00a0weeks of treatment, haemodynamic and echocardiographic assessments were performed, and tissue samples were collected for protein expression and histological analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>At week 7, no difference in RVSP or RV hypertrophy was observed between vehicle and Trep\u2010100; however, Trep\u2010810 significantly reduced RVSP and RV hypertrophy. Trep\u2010810 treatment significantly improved cardiac structure and function. Further, a short\u2010term infusion of treprostinil in rats with established PAH at 4\u00a0weeks post\u2010SU produced an acute, dose\u2010dependent reduction in RVSP consistent with a vasodilator effect. However, chronic Trep\u2010810 treatment did not alter media wall thickness, degree of vascular occlusion or total vessel count in the lungs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Treprostinil exerts therapeutic benefits in PAH through decreased vascular resistance and improved cardiac structure and function; however, treprostinil treatment does not have direct impact vascular remodelling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14472","type":"journal-article","created":{"date-parts":[[2018,8,11]],"date-time":"2018-08-11T03:10:05Z","timestamp":1533957005000},"page":"3976-3989","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Efficacy of treprostinil in the SU5416\u2010hypoxia model of severe pulmonary arterial hypertension: haemodynamic benefits are not associated with improvements in arterial remodelling"],"prefix":"10.1111","volume":"175","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1725-7438","authenticated-orcid":false,"given":"Ketul R","family":"Chaudhary","sequence":"first","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine Ottawa Hospital Research Institute  Ottawa ON Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yupu","family":"Deng","sequence":"additional","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine Ottawa Hospital Research Institute  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin M","family":"Suen","sequence":"additional","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine Ottawa Hospital Research Institute  Ottawa ON Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad","family":"Taha","sequence":"additional","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine Ottawa Hospital Research Institute  Ottawa ON Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas H","family":"Petersen","sequence":"additional","affiliation":[{"name":"United Therapeutics Corp., Research Triangle Park  NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley H J","family":"Mei","sequence":"additional","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine Ottawa Hospital Research Institute  Ottawa ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9113-8691","authenticated-orcid":false,"given":"Duncan J","family":"Stewart","sequence":"additional","affiliation":[{"name":"Sinclair Centre for Regenerative Medicine Ottawa Hospital Research Institute  Ottawa ON Canada"},{"name":"Department of Cellular and Molecular Medicine, Faculty of Medicine University of Ottawa  Ottawa ON 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