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Genetic deletion of CMG2 exacerbates systemic‐to‐pulmonary shunt‐induced pulmonary arterial hypertension
Author(s) -
Meng Liukun,
Yuan Wen,
Chi Hongjie,
Han Ruijuan,
Zhang Yeping,
Pan Xiangbin,
Meng Jian,
Liu Ying,
Song Jiawei,
Zhong Jiuchang,
Liu Xiaoyan
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000299r
Subject(s) - cardiology , shunt (medical) , pulmonary hypertension , medicine
Pulmonary arterial hypertension (PAH) secondary to congenital heart disease (CHD‐PAH) with systemic‐to‐pulmonary shunt (SPS) is characterized by proliferative vascular remodeling. Capillary morphogenesis gene‐2 (CMG2) plays a key role in cell proliferation and apoptosis. This study aimed to determine the role of CMG2 in the pathogenesis of SPS‐induced PAH. CMG2 levels were significantly downregulated in pulmonary arterioles from patients with Eisenmenger syndrome and rats with SPS‐induced PAH. CMG2 was highly expressed in several cells including human pulmonary arterial smooth muscle cells (HPASMCs). CMG2 −/− rats exhibited more severe PAH and pulmonary vascular remodeling than wild‐type rats when exposed to SPS for 8 weeks. Overexpression of CMG2 significantly inhibited proliferation and promoted apoptosis of HPASMCs, while knockdown of CMG2 promoted cell proliferation and inhibited cell apoptosis. Next‐generation sequencing and subsequent validation results suggested that PI3K‐AKT was the most prominent signaling pathway regulated by differentially expressed genes (DEGs) in CMG2 −/− rat lungs. Our work identified a novel role for CMG2 in SPS‐induced PAH based on the findings that CMG2 deficiency exacerbates SPS‐induced vascular remodeling in the development of PAH, indicating that CMG2 might act as a potential target for the treatment of CHD‐PAH.