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We assessed the safety, feasibility, and efficiency of acid ceramidase gene transfer in a rodent PH model.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A model of PH was established by the combination of left pneumonectomy and injection of Sugen toxin. Magnetic resonance imaging and right heart catheterization confirmed development of PH. Animals were subjected to intratracheal administration of synthetic adeno-associated viral vector (Anc80L65) carrying the acid ceramidase (Anc80L65.AC), an empty capsid vector, or saline. Therapeutic efficacy was evaluated 8\u00a0weeks after gene delivery.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Hemodynamic assessment 4\u00a0weeks after PH model the development demonstrated an increase in the mean pulmonary artery pressure to 30.4\u2009\u00b1\u20092.13\u00a0mmHg versus 10.4\u2009\u00b1\u20091.65\u00a0mmHg in sham (p\u2009&lt;\u20090.001), which was consistent with the definition of PH. We documented a significant increase in pulmonary vascular resistance in the saline-treated (6.79\u2009\u00b1\u20090.85\u00a0mm Hg) and empty capsid (6.94\u2009\u00b1\u20090.47\u00a0mm Hg) groups, but not in animals receiving Anc80L65.AC (4.44\u2009\u00b1\u20090.71\u00a0mm Hg, p\u2009&lt;\u20090.001). Morphometric analysis demonstrated an increase in medial wall thickness in control groups in comparison to those treated with acid ceramidase. After acid ceramidase gene delivery, a significant decrease of pro-inflammatory factors, interleukins, and senescence markers was observed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Gene delivery of acid ceramidase provided tropism to pulmonary tissue and ameliorated vascular remodeling with right ventricular dysfunction in pulmonary hypertension.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical Abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1186\/s12931-023-02487-2","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T09:02:04Z","timestamp":1691744524000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Acid ceramidase gene therapy ameliorates pulmonary arterial hypertension with right heart dysfunction"],"prefix":"10.1186","volume":"24","author":[{"given":"Michael G.","family":"Katz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoav","family":"Hadas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Vincek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Freage-Kahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nataly","family":"Shtraizent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeko M.","family":"Madjarov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Pastuszko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efrat","family":"Eliyahu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"2487_CR1","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1183\/09059180.00007814","volume":"23","author":"MM Hoeper","year":"2014","unstructured":"Hoeper MM, Gibbs SR. 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