{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:19:11Z","timestamp":1790180351444,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,7,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Pulmonary hypertension (\n              <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>\n              ) results in increased right ventricular (\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              ) afterload and ventricular remodeling. Sacubitril\/valsartan (sac\/val) is a dual acting drug, composed of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker valsartan, that has shown promising outcomes in reducing the risk of death and hospitalization for chronic systolic left ventricular heart failure. In this study, we aimed to examine if angiotensin receptor\u2010neprilysin inhibition using sac\/val attenuates\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              remodeling in\n              <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>\n              .\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              pressure overload was induced in Sprague\u2013Dawley rats via banding the main pulmonary artery. Three different cohorts of controls, placebo\u2010treated\n              <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>\n              , and sac\/val\u2010treated\n              <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>\n              were studied in a 21\u2010day treatment window. Terminal invasive hemodynamic measurements, quantitative histological analysis, biaxial mechanical testing, and constitutive modeling were employed to conduct a multiscale analysis on the effects of sac\/val on\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              remodeling in\n              <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>\n              . Sac\/val treatment decreased\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              maximum pressures (29% improvement,\n              <jats:italic>P<\/jats:italic>\n              =0.002), improved\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              contractile (30%,\n              <jats:italic>P<\/jats:italic>\n              =0.012) and relaxation (29%,\n              <jats:italic>P<\/jats:italic>\n              =0.043) functions, reduced\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              afterload (35% improvement,\n              <jats:italic>P<\/jats:italic>\n              =0.016), and prevented\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              \u2010\n              <jats:styled-content style=\"fixed-case\">pulmonary artery<\/jats:styled-content>\n              uncoupling. Furthermore, sac\/val attenuated\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              hypertrophy (16% improvement,\n              <jats:italic>P<\/jats:italic>\n              =0.006) and prevented transmural reorientation of\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              collagen and myofibers (\n              <jats:italic>P<\/jats:italic>\n              =0.011). The combined natriuresis and vasodilation resulting from sac\/val led to improved\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              biomechanical properties and prevented increased myofiber stiffness in\n              <jats:styled-content style=\"fixed-case\">PH<\/jats:styled-content>\n              (61% improvement,\n              <jats:italic>P<\/jats:italic>\n              =0.032).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Sac\/val may prevent maladaptive\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              remodeling in a pressure overload model via amelioration of\n              <jats:styled-content style=\"fixed-case\">RV<\/jats:styled-content>\n              pressure rise, hypertrophy, collagen, and myofiber reorientation as well as tissue stiffening both at the tissue and myofiber level.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.015708","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T10:16:52Z","timestamp":1592475412000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":66,"title":["Angiotensin Receptor\u2010Neprilysin Inhibition Attenuates Right Ventricular Remodeling in Pulmonary Hypertension"],"prefix":"10.1161","volume":"9","author":[{"given":"Danial","family":"Sharifi Kia","sequence":"first","affiliation":[{"name":"Department of BioengineeringUniversity of PittsburghPA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Benza","sequence":"additional","affiliation":[{"name":"Heart and Vascular InstituteUniversity of Pittsburgh Medical Center (UPMC)Pittsburgh PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy 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