{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T17:46:11Z","timestamp":1775843171383,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T00:00:00Z","timestamp":1655942400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81570365"],"award-info":[{"award-number":["81570365"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20211019"],"award-info":[{"award-number":["BK20211019"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pulmonary artery hypertension (PAH) is a common disease that threatens human health. At present, no treatment can cure PAH, and the prognosis is poor. Therefore, it is important to determine new targets for PAH treatment. Recently, a novel endogenous ligand Apela (ELABELA\/Toddler\/ELA32) of apelin peptide jejunum (APJ) receptor was identified as a possible PAH target. This study explored the potential effect of Apela gene therapy on rats with PAH. An AAV\u2010ELA32 recombinant expression vector was constructed by molecular cloning. Purified adeno\u2010associated virus (AAV) was injected into monocrotaline (MCT)\u2010induced PAH rats via tail vein 1 and 2\u2009weeks after modeling. Apela gene therapy significantly reduced the increased right ventricular systolic pressure and N\u2010terminal pro\u2010brain natriuretic peptide (NT\u2010proBNP) in PAH rats. The results of histopathology and immunofluorescence showed that Apela gene therapy not only reduced the rate of pulmonary arteriole muscularization and media thickening in PAH rats but also inhibited the endothelial\u2010to\u2010mesenchymal transition of the pulmonary arteriole. Western blotting showed that Apela gene therapy up\u2010regulated the expression of KLF2\/eNOs and BMPRII\/SMAD4 in pulmonary arterioles of PAH rats. Overall, the results show that Apela gene therapy can inhibit pulmonary arteriolar vascular remodeling and reduce pulmonary artery pressure in PAH rats. These effects may be related to KLF2\/eNOs and BMPRII\/SMAD4 signaling pathways. The apelinergic system may be a potential new target for the prevention and treatment of PAH.<\/jats:p>","DOI":"10.1096\/fj.202200266r","type":"journal-article","created":{"date-parts":[[2022,6,24]],"date-time":"2022-06-24T02:19:00Z","timestamp":1656037140000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Apela gene therapy alleviates pulmonary hypertension in rats"],"prefix":"10.1096","volume":"36","author":[{"given":"Yuexin","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"},{"name":"Department of Pathology Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangli","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"},{"name":"Department of Pathology Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"},{"name":"Department of Pathology Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jue","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing China"},{"name":"Department of Pathology Affiliated Nanjing Brain Hospital, Nanjing Medical University  Nanjing 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