1.Research progress in hypoxia-induced endothelial-to-mesenchymal transition induced pulmonary vascular remodeling and drug interventions
Hongmai WANG ; Qingqing XIA ; Xiangyun GAI ; Jinyu WANG ; Yuefu ZHAO
Chinese Journal of Pharmacology and Toxicology 2024;38(3):232-240
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.
2.Distribution of vascular endothelial growth factor gene polymorphism in Uyghur Ethnic patients with urolithiasis in south Xinjiang
Yuefu HAN ; Qinzhang WANG ; Guofu DING ; Biao QIAN ; Jiangping WANG ; Yinglong LI ; Zhao NI ; Xinmin WANG ; Shunming XIE ; Wenxiao WANG ; Zongyue CHEN ; Guodong ZHU ; Shiqi JI ; Yujie WANG ; Niwaer AN ; Guanglu SONG ; Hui WEI ; Qunying ZHANG
Chinese Journal of Urology 2010;31(9):601-603
Objective To determine vascular endothelial growth factor(VEGF)-460 gene polymorphism in Uyghurs and its relationship to urolithiasis in south Xinjiang. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP),gene sequencing and genetic analysis methods were used in 200 urolithiasis patients of Uyghurs, and 200 healthy Uyghurs. Results The distribution of genotype and allele had no significant difference between urolithiasis patients and normal controls (P>0. 05). The frequencies for the CC,TT and CT genotypes in patients with urolithiasis and normal controls were 1.5 %, 29.0 %, 69.5 % and 0. 5 %, 27.5 %, 72.0 %, respectively. The frequencies for C and T allele were 36.2%,63.7% and 36.9% ,63.1%, respectively. Conclusions The results of VEGF-460 gene polymorphisms indicate no significant relationship between patients with turolithiasis and normal controls in Uyghurs in south Xinjiang,which may not be urolithiasis susceptibility genetic locus.