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Capillary morphogenesis gene\u20102 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS\u2010induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS\u2010induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rats exhibited more severe PAH and pulmonary vascular remodeling than wild\u2010type rats when exposed to SPS for 8\u00a0weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next\u2010generation sequencing and subsequent validation results suggested that PI3K\u2010AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    rat lungs. Our work identified a novel role for CMG2 in SPS\u2010induced PAH based on the findings that CMG2 deficiency exacerbates SPS\u2010induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD\u2010PAH.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000299r","type":"journal-article","created":{"date-parts":[[2021,3,22]],"date-time":"2021-03-22T10:32:19Z","timestamp":1616409139000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Genetic deletion of CMG2 exacerbates systemic\u2010to\u2010pulmonary shunt\u2010induced pulmonary arterial hypertension"],"prefix":"10.1096","volume":"35","author":[{"given":"Liukun","family":"Meng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Cardiovascular Disease Fuwai Hospital National Center for Cardiovascular Disease Peking Union Medical College Chinese Academy of Medical Sciences Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Yuan","sequence":"additional","affiliation":[{"name":"Medical Research Center &amp; 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