{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:15:59Z","timestamp":1791918959047,"version":"4.3.4"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Intrauterine growth restriction (IUGR) is closely related to systemic or pulmonary hypertension (PH) in adulthood. Aberrant crosstalk between pulmonary vascular endothelial cells (PVECs) and pulmonary arterial smooth muscle cells (PASMCs) that is mediated by exosomes plays an essential role in the progression of PH. FoxM1 (Forkhead box M1) is a key transcription factor that governs many important biological processes.<\/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\">IUGR\u2010induced PH rat models were established. Transwell plates were used to coculture PVECs and PASMCs. Exosomes were isolated from PVEC\u2010derived medium, and a microRNA (miRNA) screening was proceeded to identify effects of IUGR on small RNAs enclosed within exosomes. Dual\u2010Luciferase assay was performed to validate the predicted binding sites of miRNAs on FoxM1 3\u2019 untranslated region. FoxM1 inhibitor thiostrepton was used in IUGR\u2010induced PH rats. In this study, we found that FoxM1 expression was remarkably increased in IUGR\u2010induced PH, and PASMCs were regulated by PVECs through FoxM1 signaling in a non\u2010contact way. An miRNA screening showed that miR\u2010214\u20103p, miR\u2010326\u20103p, and miR\u2010125b\u20102\u20103p were downregulated in PVEC\u2010derived exosomes of the IUGR group, which were associated with overexpression of FoxM1 and more significant proliferation and migration of PASMCs. Dual\u2010Luciferase assay demonstrated that the 3 miRNAs directly targeted FoxM1 3\u2019 untranslated region. FoxM1 inhibition blocked the PVECs\u2010PASMCs crosstalk and reversed the abnormal functions of PASMCs. In vivo, treatment with thiostrepton significantly reduced the severity of PH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Transmission of exosomal miRNAs from PVECs regulated the functions of PASMCs via FoxM1 signaling, and FoxM1 may serve as a potential therapeutic target in IUGR\u2010induced PH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027177","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T10:56:19Z","timestamp":1671447379000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["PVECs\u2010Derived Exosomal microRNAs Regulate PASMCs via FoxM1 Signaling in IUGR\u2010induced Pulmonary Hypertension"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1667-5048","authenticated-orcid":false,"given":"Xiaofei","family":"Luo","sequence":"first","affiliation":[{"name":"Department of Neonatology, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-7541","authenticated-orcid":false,"given":"Chengcheng","family":"Hang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8097-6569","authenticated-orcid":false,"given":"Ziming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2592-0992","authenticated-orcid":false,"given":"Kaixing","family":"Le","sequence":"additional","affiliation":[{"name":"Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1831-254X","authenticated-orcid":false,"given":"Yuhan","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9312-607X","authenticated-orcid":false,"given":"Ying","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pediatric Health Care, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2813-5463","authenticated-orcid":false,"given":"Lingling","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The First Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-2719","authenticated-orcid":false,"given":"Yajie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6676-0983","authenticated-orcid":false,"given":"Lixia","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Neonatology, The Children\u2019s Hospital Zhejiang University School of Medicine, National Clinical Research Center for Child Health Hangzhou Zhejiang Province People\u2019s Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7148-846X","authenticated-orcid":false,"given":"Xuefeng","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology Immunology &amp; 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