The effect and mechanism of YAP1 expression on placental angiogenesis in preeclampsia exposed to hypoxia environment

Yixia Pan; Rui Liu; Chan Wei; Qiang MA; Weimin Wang

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The effect and mechanism of YAP1 expression on placental angiogenesis in preeclampsia exposed to hypoxia environment

VernacularTitle:缺氧环境下YAP1的表达对子痫前期胎盘血管形成的影响及作用机制
Author: Yixia PAN ¹ ; Rui LIU ² ; Chan WEI ³ ; Qiang MA ⁴ ; Weimin WANG ¹
Author Information

1. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061
2. Obstetrics and Gynecology Hospital Affiliated to Medical College of Zhejiang University, Hangzhou 310012
3. Maternal and Child Health Care and Family Planning Service Center in Chang’an District of Xi’an City, Xi’an 710100
4. Department of Vascular Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China
Publication Type:Journal Article
Keywords: preeclampsia; hypoxia; YAP1; human umbilical vein endothelial cell; apoptosis; invasion; angiogenesis
From: Journal of Xi'an Jiaotong University(Medical Sciences) 2021;42(4):547-553
CountryChina
Language:Chinese
Abstract: 【Objective】 To investigate the effect and mechanism of inhibiting Yes-associated protein1 (YAP1) expression by verteporfin on proliferation, migration and invasion of human umbilical vein endothelial cells (HUVECs) exposed to hypoxia environment and the possible mechanisms that further affect placental angiogenesis in preeclampsia. 【Methods】 MTT method was used to detect the cell viability of HUVECs at different concentrations (0, 4, 8, 12 and 16 μg/mL) after 12 h and 24 h treatment with verteporfin under hypoxia and calculate the IC50 value to select the subsequent experimental drug concentration. Flow cytometry was made to analyze verteporfin’s effect on HUVEC apoptosis in hypoxic environment. The wound healing assay and Transwell invasion assay were used to determine the effect of verteporfin on HUVEC cell migration and invasion abilities under hypoxic environment. Angiogenesis test was used to detect the effect of verteporfin on the angiogenesis of HUVECs under hypoxic environment. The effects of verteporfin on the expression levels of YAP1 and TEAD1 in Hippo signaling pathway under normoxia and hypoxia were determined by Western blotting. 【Results】 Under hypoxic environment, verteporfin could inhibit the proliferation of HUVECs by calculating the IC50 value, the subsequent experimental group selected 16 μg/mL verteporfin to treat cells. Flow cytometry showed that verteporfin induced the apoptosis rate of HUVECs under hypoxia (P<0.01). The results of wound healing, Transwell invasion and the angiogenesis experiments confirmed that compared with the control group, verteporfin could inhibit the migration, invasion and angiogenesis of HUVECs in hypoxic environment (P<0.05). Western blotting assay indicated that under normoxia and hypoxia, the expressions of YAP1 and TEAD1 were reduced (P<0.01). 【Conclusion】 In hypoxic environment, verteporfin inhibits the proliferation of HUVECs by inhibiting the expressions of YAP1 and TEAD1, and reduces the migration, invasion and angiogenesis of HUVECs. It is confirmed that the Hippo-YAP1 signaling pathway may affect the placental angiogenesis of preeclampsia and participate in the occurrence of preeclampsia by regulating the proliferation and invasion of vascular endothelial cells.