{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:41:15Z","timestamp":1792730475792,"version":"4.5.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,3,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Pulmonary hypertension (PH) results in increased right ventricular (RV) afterload, leading to RV dysfunction and failure. The mechanisms underlying maladaptive RV remodeling are poorly understood. In this study, we investigated the multiscale and mechanistic nature of RV free\u2010wall (RVFW) biomechanical remodeling and its correlations with RV function adaptations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">Mild and severe models of PH, consisting of a hypoxia model in Sprague\u2013Dawley rats (n=6 each, control and PH) and a Sugen\u2010hypoxia model in Fischer rats (n=6 each, control and PH), were used. Organ\u2010level function, tissue\u2010level stiffness, and microstructure were quantified through in\u00a0vivo and ex\u00a0vivo measures, respectively. Multiscale analysis was used to determine the association between fiber\u2010level remodeling, tissue\u2010level stiffness and anisotropy, and organ\u2010level dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">Decreased RV\u2013pulmonary artery coupling correlated strongly with RVFW stiffening but showed a weaker association with the loss of RVFW anisotropy. Machine\u2010learning classification identified the range of adaptive and maladaptive RVFW stiffening. Multiscale modeling revealed that increased collagen fiber tautness was a key remodeling mechanism that differentiated severe from mild stiffening. Myofiber orientation analysis indicated a shift away from the predominantly circumferential fibers observed in healthy RVFW specimens, leading to a significant loss of tissue anisotropy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Multiscale biomechanical analysis indicated that, although hypertrophy and fibrosis occur in both mild and severe PH, certain fiber\u2010level remodeling events, including increased tautness of collagen fibers and significant reorientations of myofibers, contributed to excessive biomechanical maladaptation of the RVFW leading to severe RV\u2013pulmonary artery uncoupling. Collagen fiber remodeling and the loss of tissue anisotropy can provide an improved understanding of the transition from adaptive to maladaptive RV remodeling.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.124.037126","type":"journal-article","created":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T06:08:34Z","timestamp":1740550114000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Right Ventricular Stiffening and Anisotropy Alterations in Pulmonary Hypertension: Mechanisms and Relations to Right Heart Failure"],"prefix":"10.1161","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5445-4070","authenticated-orcid":false,"given":"Sunder","family":"Neelakantan","sequence":"first","affiliation":[{"name":"Texas A&M University","place":["College Station, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5691-781X","authenticated-orcid":false,"given":"Alexander","family":"Vang","sequence":"additional","affiliation":[{"name":"Providence VA Medical Center","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9008-9058","authenticated-orcid":false,"given":"Rana Raza","family":"Mehdi","sequence":"additional","affiliation":[{"name":"Texas A&M University","place":["College Station, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3230-7731","authenticated-orcid":false,"given":"Haley","family":"Phelan","sequence":"additional","affiliation":[{"name":"Texas A&M University","place":["College Station, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0374-6612","authenticated-orcid":false,"given":"Preston","family":"Nicely","sequence":"additional","affiliation":[{"name":"Alpert Medical School of Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2089-8244","authenticated-orcid":false,"given":"Tasnim","family":"Imran","sequence":"additional","affiliation":[{"name":"Providence VA Medical Center","place":["Providence, USA"]},{"name":"Alpert Medical School of Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-5384","authenticated-orcid":false,"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Providence VA Medical Center","place":["Providence, USA"]},{"name":"Alpert Medical School of Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-5481","authenticated-orcid":false,"given":"Gaurav","family":"Choudhary","sequence":"additional","affiliation":[{"name":"Providence VA Medical Center","place":["Providence, USA"]},{"name":"Alpert Medical School of Brown University","place":["Providence, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9787-1117","authenticated-orcid":false,"given":"Reza","family":"Avazmohammadi","sequence":"additional","affiliation":[{"name":"Texas A&M University","place":["College Station, USA"]},{"name":"Texas A&M University","place":["Houston, USA"]},{"name":"Houston Methodist Academic Institute","place":["Houston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","first-page":"73","article-title":"Pulmonary hypertension","volume":"114","author":"Hoeper MM","year":"2017","unstructured":"Hoeper MM, Ghofrani HA, Grunig E, Klose H, Olschewski H, Rosenkranz S. 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