{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T13:46:55Z","timestamp":1772891215290,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T00:00:00Z","timestamp":1652313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Investigator Sponsored Study (ISS)","award":["R01HL148712"],"award-info":[{"award-number":["R01HL148712"]}]},{"name":"Investigator Sponsored Study (ISS)","award":["15SDG24910003"],"award-info":[{"award-number":["15SDG24910003"]}]},{"name":"Investigator Sponsored Study (ISS)","award":["RG-515656"],"award-info":[{"award-number":["RG-515656"]}]},{"name":"NIH\/NHLBI","award":["R01HL148712"],"award-info":[{"award-number":["R01HL148712"]}]},{"name":"NIH\/NHLBI","award":["15SDG24910003"],"award-info":[{"award-number":["15SDG24910003"]}]},{"name":"NIH\/NHLBI","award":["RG-515656"],"award-info":[{"award-number":["RG-515656"]}]},{"name":"American Heart Association Scientist Development","award":["R01HL148712"],"award-info":[{"award-number":["R01HL148712"]}]},{"name":"American Heart Association Scientist Development","award":["15SDG24910003"],"award-info":[{"award-number":["15SDG24910003"]}]},{"name":"American Heart Association Scientist Development","award":["RG-515656"],"award-info":[{"award-number":["RG-515656"]}]},{"name":"American Lung Association Biomedical Research","award":["R01HL148712"],"award-info":[{"award-number":["R01HL148712"]}]},{"name":"American Lung Association Biomedical Research","award":["15SDG24910003"],"award-info":[{"award-number":["15SDG24910003"]}]},{"name":"American Lung Association Biomedical Research","award":["RG-515656"],"award-info":[{"award-number":["RG-515656"]}]},{"name":"Vitalant and the Hemophilia Center of Western Pennsylvania","award":["R01HL148712"],"award-info":[{"award-number":["R01HL148712"]}]},{"name":"Vitalant and the Hemophilia Center of Western Pennsylvania","award":["15SDG24910003"],"award-info":[{"award-number":["15SDG24910003"]}]},{"name":"Vitalant and the Hemophilia Center of Western Pennsylvania","award":["RG-515656"],"award-info":[{"award-number":["RG-515656"]}]},{"name":"Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute","award":["R01HL148712"],"award-info":[{"award-number":["R01HL148712"]}]},{"name":"Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute","award":["15SDG24910003"],"award-info":[{"award-number":["15SDG24910003"]}]},{"name":"Pittsburgh Heart, Lung, and Blood Vascular Medicine Institute","award":["RG-515656"],"award-info":[{"award-number":["RG-515656"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Prostacyclin analogs are among the most effective and widely used therapies for pulmonary arterial hypertension (PAH). However, it is unknown whether they also confer protection through right ventricle (RV) myocardio-specific mechanisms. Moreover, the use of prostacyclin analogs in severe models of PAH has not been adequately tested. To further identify underlying responses to prostacyclin, a prostacyclin analogue, treprostinil, was used in a preclinical rat Sugen-chronic hypoxia (SuCH) model of severe PAH that closely resembles the human disease. Male Sprague\u2013Dawley rats were implanted with osmotic pumps containing vehicle or treprostinil, injected concurrently with a bolus of Sugen (SU5416) and exposed to 3-week hypoxia followed by 3-week normoxia. RV function was assessed using pressure\u2013volume loops and hypertrophy by weight assessed. To identify altered mechanisms within the RV, tissue samples were used to perform a custom RNA array analysis, histological staining, and protein and transcript level confirmatory analyses. Treprostinil significantly reduced SuCH-associated RV hypertrophy and decreased the rise in RV systolic pressure, mean pulmonary arterial (mPAP), and right atrial (RAP) pressure. Prostacyclin treatment was associated with improvements in RV stroke work, maximum rate of ventricular pressure change (max dP\/dt) and the contractile index, and almost a complete reversal of SuCH-associated increase in RV end-systolic elastance, suggesting the involvement of load-independent improvements in intrinsic RV systolic contractility by prostacyclin treatment. An analysis of the RV tissues showed no changes in cardiac mitochondrial respiration and ATP generation. However, custom RNA array analysis revealed amelioration of SuCH-associated increases in newly identified TBX20 as well as the fibrotic markers collagen1\u03b11 and collagen 3\u03b11 upon treprostinil treatment. Taken together, our data support decreased afterload and load-independent improvements in RV function following prostacyclin administration in severe PAH, and these changes appear to associate with improvements in RV fibrotic responses.<\/jats:p>","DOI":"10.3390\/ijms23105426","type":"journal-article","created":{"date-parts":[[2022,5,12]],"date-time":"2022-05-12T21:46:53Z","timestamp":1652392013000},"page":"5426","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Reversal of Right Ventricular Hypertrophy and Dysfunction by Prostacyclin in a Rat Model of Severe Pulmonary Arterial Hypertension"],"prefix":"10.3390","volume":"23","author":[{"given":"Rebecca R.","family":"Vanderpool","sequence":"first","affiliation":[{"name":"Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia","family":"Gorelova","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiran","family":"Ma","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Division of Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Alhamaydeh","sequence":"additional","affiliation":[{"name":"Brody School of Medicine, East Carolina University, Greenville, NC 27834, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Baust","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sruti","family":"Shiva","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stevan P.","family":"Tofovic","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Hu","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seyed Mehdi","family":"Nouraie","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Division of Pulmonary, Allergy & Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark T.","family":"Gladwin","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Division of Pulmonary, Allergy & Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Sharifi-Sanjani","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Division of Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0386-5360","authenticated-orcid":false,"given":"Imad","family":"Al Ghouleh","sequence":"additional","affiliation":[{"name":"Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA"},{"name":"Division of Cardiology, 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