{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T23:58:14Z","timestamp":1792022294749,"version":"4.4.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["PJT-425751"],"award-info":[{"award-number":["PJT-425751"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["PJT-462950"],"award-info":[{"award-number":["PJT-462950"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["PJT-166151"],"award-info":[{"award-number":["PJT-166151"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 HL080494"],"award-info":[{"award-number":["R01 HL080494"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5U01HL098147"],"award-info":[{"award-number":["5U01HL098147"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institute of Health Research","doi-asserted-by":"crossref","award":["PJT-183758"],"award-info":[{"award-number":["PJT-183758"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Pulmonary arterial hypertension (PAH) is a progressive vascular syndrome characterized by aberrant signaling, severe pulmonary artery remodeling, and right ventricular (RV) failure, a major driver of morbidity and mortality. Dysregulation of the apelinergic pathway has been implicated in pulmonary vascular remodeling in PAH. Using a sugen-hypoxia rat model of PAH, we assessed the ability of a novel apelin analog, resistant to native peptidase degradation, to reverse the pathological hallmarks of PAH and RV dysfunction. Apelin analog therapy corrected the vascular lesions in the lungs and nearly normalized pulmonary arterial pressures. Early cardiorenal syndrome, RV dilation and dysfunction as well as RV cardiomyocyte and fibroblast activation induced by pressure overload, were also reversed by apelin analog treatment. Single-nucleus RNA sequencing of the lungs and RV revealed apelin-analog treatment activated several protective pathways, including rebalancing protective BMPR2 (bone morphogenetic protein receptor type 2) signaling to counteract excessive pathogenic TGFBR2 (transforming growth factor \u03b2 receptor 2) activity in PAH. These findings highlight the therapeutic potential of exogenous apelin in reversing pulmonary vascular and cardiac pathologies in PAH and support further investigation to evaluate the clinical benefits of apelin analog treatment in patients with PAH and RV failure.<\/jats:p>","DOI":"10.1172\/jci.insight.200684","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:00:36Z","timestamp":1781798436000},"source":"Crossref","is-referenced-by-count":1,"title":["Apelin analog treatment reverses severe pulmonary arterial hypertension and right ventricular heart failure"],"prefix":"10.1172","author":[{"given":"Jennie","family":"Vu","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Alberta, Edmonton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Zhabyeyev","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, 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C.","family":"Chappell","sequence":"additional","affiliation":[{"name":"Department of Surgery\/Hypertension and Vascular Research, Wake Forest University School of Medicine, Winston Salem, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5978-5779","authenticated-orcid":true,"given":"Yuri","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1128-0100","authenticated-orcid":true,"given":"Michel","family":"Bouvier","sequence":"additional","affiliation":[{"name":"Institute for Research in Immunology and Cancer, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, 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