{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:01:21Z","timestamp":1791806481579,"version":"4.3.4"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Pulmonary hypertension, characterized by vascular remodeling, currently lacks curative therapeutic options. The dysfunction of pulmonary artery endothelial cells plays a pivotal role in the initiation and progression of pulmonary hypertension (PH). ErbB3 (human epidermal growth factor receptor 3), also recognized as HER3, is a member of the ErbB family of receptor tyrosine kinases.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>Microarray, immunofluorescence, and Western blotting analyses were conducted to investigate the pathological role of ErbB3. Blood samples were collected for biomarker examination from healthy donors or patients with hypoxic PH. The pathological functions of ErbB3 were further validated in rodents subjected to chronic hypoxia- and Sugen-induced PH, with or without adeno-associated virus-mediated ErbB3 overexpression, systemic deletion, or endothelial cell\u2013specific ErbB3 knockdown. Primary human pulmonary artery endothelial cells and pulmonary artery smooth muscle cells were used to elucidate the underlying mechanisms.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>ErbB3 exhibited significant upregulation in the serum, lungs, distal pulmonary arteries, and pulmonary artery endothelial cells isolated from patients with PH compared with those from healthy donors. ErbB3 overexpression stimulated hypoxia-induced endothelial cell proliferation, exacerbated pulmonary artery remodeling, elevated systolic pressure in the right ventricle, and promoted right ventricular hypertrophy in murine models of PH. Conversely, systemic deletion or endothelial cell\u2013specific knockout of ErbB3 yielded opposite effects. Coimmunoprecipitation and proteomic analysis identified YB-1 (Y-box binding protein 1) as a downstream target of ErbB3. ErbB3 induced nuclear translocation of YB-1 and subsequently promoted hypoxia-inducible factor 1\/2\u03b1 transcription. A positive loop involving ErbB3-periostin-hypoxia\u2013inducible factor 1\/2\u03b1 was identified to mediate the progressive development of this disease. MM-121, a human anti-ErbB3 monoclonal antibody, exhibited both preventive and therapeutic effects against hypoxia-induced PH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our study reveals, for the first time, that ErbB3 serves as a novel biomarker and a promising target for the treatment of PH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.123.067005","type":"journal-article","created":{"date-parts":[[2024,1,12]],"date-time":"2024-01-12T10:00:29Z","timestamp":1705053629000},"page":"1533-1553","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["ErbB3 Governs Endothelial Dysfunction in Hypoxia-Induced Pulmonary Hypertension"],"prefix":"10.1161","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8000-3356","authenticated-orcid":true,"given":"Jin-Song","family":"Bian","sequence":"first","affiliation":[{"name":"Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People\u2019s Hospital (the First Affiliated Hospital, Southern University of Science and Technology; the Second Clinical Medical College, Jinan University), China (J.-S.B., J.Z., Y.L., R.C., X.N.)."},{"name":"Department of Pharmacology, Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases, School of Medicine, Southern University of Science and Technology, China (J.-S.B., L.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-9749","authenticated-orcid":true,"given":"Jingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Lung Transplant Group, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, China (J.C., J.T., Y.C., X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8830-628X","authenticated-orcid":true,"given":"Junting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People\u2019s Hospital (the First Affiliated Hospital, Southern University of Science and Technology; the Second Clinical Medical College, Jinan University), China (J.-S.B., J.Z., Y.L., R.C., X.N.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1041-561X","authenticated-orcid":true,"given":"Jianxin","family":"Tan","sequence":"additional","affiliation":[{"name":"Lung Transplant Group, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, China (J.C., J.T., Y.C., X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Lung Transplant Group, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, China (J.C., J.T., Y.C., X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xusheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Lung Transplant Group, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, China (J.C., J.T., Y.C., X.Y.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Shenzhen Respiratory Disease, Shenzhen Institute of Respiratory Disease, Shenzhen People\u2019s Hospital (the First Affiliated Hospital, Southern University of Science and Technology; 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