Reactive Oxygen Species are Essential for Placental Angiogenesis During Early Gestation

作者全名："Yang, Yike; Jin, Huili; Qiu, Yuhan; Liu, Yamin; Wen, Li; Fu, Yong; Qi, Hongbo; Baker, Philip N.; Tong, Chao"

作者地址："[Yang, Yike; Jin, Huili; Wen, Li; Fu, Yong; Qi, Hongbo; Tong, Chao] Chongqing Med Univ, State Key Lab Maternal & Fetal Med Chongqing Munic, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Yang, Yike] Peking Univ, Dept Obstet, Hosp 3, Beijing 100191, Peoples R China; [Jin, Huili] Guizhou Med Univ, Dept Obstet, Affiliated Hosp, Guiyang 550004, Peoples R China; [Qiu, Yuhan] Chongqing Med Univ, Dept Obstet & Gynecol, Second Affiliated Hosp, Chongqing 400010, Peoples R China; [Liu, Yamin; Qi, Hongbo] Chongqing Med Univ, Dept Obstet, Women & Childrens Hosp, Chongqing 401147, Peoples R China; [Baker, Philip N.] Univ Leicester, Coll Life Sci, Leicester LE1 7RH, England"

通信作者："Fu, Y; Qi, HB; Tong, C (通讯作者)，Chongqing Med Univ, State Key Lab Maternal & Fetal Med Chongqing Munic, Affiliated Hosp 1, Chongqing 400016, Peoples R China.; Qi, HB (通讯作者)，Chongqing Med Univ, Dept Obstet, Women & Childrens Hosp, Chongqing 401147, Peoples R China."

来源：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000810924900002

JCR分区：Q2

影响因子：7.31

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："Background. Preeclampsia (PE) is associated with insufficient placental perfusion attributed to maldevelopment of the placental vasculature. Reactive oxygen species (ROS) are implicated in angiogenesis, but their regulatory effects and mechanisms in placental vascular development remain unclear. Methods. Placental oxidative stress was determined throughout gestation by measuring 4-hydroxynonenal (4HNE) and malondialdehyde (MDA). The antioxidant MitoQ was administered to pregnant mice from GDs 7.5 to 11.5; placental morphology and angiogenesis pathways were examined on GDs 11.5 and 18.5. Moreover, we established a mouse mFlt-1-induced PE model and assessed blood pressure, urine protein levels, and placental vascular development on GDs 11.5 and 18.5. Human umbilical vein endothelial cells (HUVECs) were treated with various H2O2 concentrations to evaluate cell viability, intracellular ROS levels, and tube formation capability. MitoQ, an AKT inhibitor and an ERK1/2 inhibitor were applied to validate the ROS-mediated mechanism regulating placental angiogenesis. Results. First-trimester placentas presented significantly higher MDA and 4HNE levels. MitoQ significantly reduced the blood vessel density and angiogenesis pathway activity in the placenta on GDs 11.5 and 18.5. Serum sFlt-1 levels were elevated, and we observed poor placental angiogenesis and PE-like symptoms in cases with mFlt-1 overexpression. Moderate H2O2 treatment promoted HUVEC proliferation and angiogenesis, whereas these improvements were abolished by MitoQ, AKT inhibitor, or ERK1/2 inhibitor treatment. Conclusions. Moderate ROS levels are essential for placental angiogenesis; diminishing ROS with potent antioxidants during placentation decreases placental angiogenesis and increases PE risk. Therefore, antioxidant therapy should be considered carefully for normal pregnant women during early gestation."

基金机构："National Natural Sciences Foundation of China [81871189, 82001580, U21A20346, 82171662]; Chongqing Science and Technology Commission [cstc2019jcyj-msxmX0856, cstc2021ycjh-bgzxm0192]; Chongqing Health Committee [2019GDRC012, 2020MSXM037]"

基金资助正文："AcknowledgmentsThis work was supported by grants from the National Natural Sciences Foundation of China (81871189, 82001580, U21A20346, and 82171662), the Chongqing Science and Technology Commission (cstc2019jcyj-msxmX0856 and cstc2021ycjh-bgzxm0192), and the Chongqing Health Committee (2019GDRC012 and 2020MSXM037)."