Research progress in hypoxia-induced endothelial-to-mesenchymal transition induced pulmonary vascular remodeling and drug interventions
10.3867/j.issn.1000-3002.2024.03.009
- VernacularTitle:低氧诱导内皮-间充质转化致肺血管重构及药物干预研究进展
- Author:
Hongmai WANG
1
;
Qingqing XIA
;
Xiangyun GAI
;
Jinyu WANG
;
Yuefu ZHAO
Author Information
1. 青海民族大学药学院,青海 西宁 810007
- Keywords:
pulmonary vascular remodeling;
hypoxia;
endothelial-to-mesenchymal transition;
pulmonary hypertension
- From:
Chinese Journal of Pharmacology and Toxicology
2024;38(3):232-240
- CountryChina
- Language:Chinese
-
Abstract:
Pulmonary hypertension(PH)is the pulmonary vascular remodeling caused by endothe-lial dysfunction and other factors,which leads to the increase of pulmonary artery pressure and finally right heart failure and patient death.Medications can significantly improve the symptoms of patients with pulmonary hypertension,but drugs can't cure vascular remodeling and right heart failure once for all,so it is urgent to find new treatments.Endothelial cells can obtain mesenchymal phenotypes after hypoxia stimulation,that is,endothelial-to-mesenchymal transition(EndMT).Increasing studies have shown that EndMT plays an important role in pulmonary vascular remodeling of PH.In this review,three signaling pathways related to induction of endothelial-to-mesenchymal transition under hypoxic conditions and research progress in related drugs are elaborated:① Transforming growth factor-β/bone morphogenetic protein(TGF-β/BMP)signaling pathway.The TGF-β/BMP pathway is mediated by Smad,and hypoxia regulates the expressions of EndMT-related genes by inhibiting or inducing the phosphorylation level of Smad in the downstream medium.② Notch signaling pathway.Hypoxia can enhance Jagged/Notch signaling pathway and promote the EndMT process.③Wnt/β-catenin signaling pathway.Hypoxia increases the expression of β-catenin,activates the Wnt signaling pathway,and regulates the expressions of EndMT regulatory genes.The significance of hypoxia-induced EndMT as an impor-tant pathogenic factor in PH is clarified in order to provide new ideas for the improvement of pulmonary vascular remodeling and recommend new effective strategies for the prevention and treatment of PH.
