{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T09:36:27Z","timestamp":1790415387891,"version":"4.1.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"French National Institute for Health and Medical Research"},{"name":"University Paris-Saclay, the Marie Lannelongue Hospital"},{"name":"French National Agency for Research","award":["ANR-16-CE17-0014"],"award-info":[{"award-number":["ANR-16-CE17-0014"]}]},{"name":"French National Agency for Research","award":["ANR-18-RHUS-0006"],"award-info":[{"award-number":["ANR-18-RHUS-0006"]}]},{"DOI":"10.13039\/501100002915","name":"Fondation de la Recherche M\u00e9dicale","doi-asserted-by":"crossref","award":["DEQ20150331712"],"award-info":[{"award-number":["DEQ20150331712"]}],"id":[{"id":"10.13039\/501100002915","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100011879","name":"LabEx LERMIT","doi-asserted-by":"publisher","award":["ANR-10-LABX-0033"],"award-info":[{"award-number":["ANR-10-LABX-0033"]}],"id":[{"id":"10.13039\/501100011879","id-type":"DOI","asserted-by":"publisher"}]},{"name":"French PAH patient association"},{"name":"french Fonds de Dotation \u2018Recherche en Sant\u00e9 Respiratoire\u2019\u2014(FRSR)\u2014\nFondation du Souffle"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Although right ventricular (RV) function is an important determinant of morbidity and mortality in patients with pulmonary arterial hypertension (PAH), there is no treatment targeting directly the RV. We evaluate the efficacy of sacubitril\/valsartan (LCZ 696) as add-on therapy to bosentan in rats with severe pulmonary hypertension (PH).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>Combination therapy of LCZ 696 and bosentan has additive vascular protective effects against the pulmonary vascular remodelling and PH in two preclinical models of severe PH. Compared with monotherapy, co-treatment of LCZ 696 (30 or 68\u2009mg\/kg\/day for 2\u2009weeks, per os) and bosentan (100\u2009mg\/kg\/day for 2\u2009weeks, per os) started 7 days after monocrotaline (MCT) injection substantially reduces pulmonary pressures, vascular remodelling, and RV hypertrophy and fibrosis in rats. Consistent with these observations, co-treatment of rats with established PH induced by sugen\/hypoxia (SuHx) with LCZ 696 (30\u2009mg\/kg\/day for 3\u2009weeks, per os) and bosentan (100\u2009mg\/kg\/day for 3\u2009weeks, per os) started 5\u2009weeks after Sugen injection partially attenuate total pulmonary vascular resistance and cardiovascular structures. We also obtained evidence showing that LCZ 696 has anti-proliferative effect on cultured human pulmonary artery smooth muscle cells derived from patients with idiopathic PAH, an effect that is more pronounced in presence of bosentan. Finally, we found that the plasma levels of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) are higher in rats co-treated with LCZ 696 (30\u2009mg\/kg\/day) and bosentan (100\u2009mg\/kg\/day) than in MCT and SuHx rats treated with vehicle.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Dual therapy with LCZ 696 plus bosentan proved significantly superior beneficial effect to LCZ 696 or bosentan alone on vascular remodelling and severity of experimental PH.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cvr\/cvaa200","type":"journal-article","created":{"date-parts":[[2020,7,3]],"date-time":"2020-07-03T19:19:23Z","timestamp":1593803963000},"page":"1391-1401","source":"Crossref","is-referenced-by-count":39,"title":["Additive protective effects of sacubitril\/valsartan and bosentan on vascular remodelling in experimental pulmonary 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