Upregulation of P53 promoted G1 arrest and apoptosis in human umbilical cord vein endothelial cells from preeclampsia.
Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality. Current research has focused on endothelial dysfunction regarding pathogenesis of preeclampsia. However, very limited or no studies so far have been performed to assess possible damaged endothelial cell growth/development in the placenta-umbilical cord circulation system in human preeclampsia.



We isolated and cultured human umbilical cord vein endothelial cells (HUVECs) from normal and preeclampsia pregnancies in vitro. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay to measure cell growth and flow cytometric analysis to determine cell-cycle distribution. Annexin V-fluorescein isothiocyanate/propidium iodide double staining was employed for cell apoptosis experiments.



The study showed that the cell growth was significantly suppressed, accompanied by the increased G1 arrest and apoptosis in cultured HUVECs from preeclampsia pregnancies comparing with normotensive controls. Protein P53 was upregulated in the cultured HUVECs from preeclampsia pregnancies, which induced G1 arrest, followed by upregulating P21 expression, and downregulating cyclin E expression and CDK2-cyclin E complexes. On the other hand, upregulation of P53 also activated Bax gene and repressed Bcl-2 and BIRC5 genes, resulting in an increase of the Bax/Bcl-2 ratio and subsequently activating caspase cascade, ultimately led to an initiation of the apoptotic machinery.



These results indicated that in preeclampsia, vascular endothelial cells could be damaged and cellular proliferation was depressed in human placenta-umbilical cord circulation, adding new information on endothelial cell injury for better understanding the pathogenesis of preeclampsia.
aInstitute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou, China bCenter for Perinatal Biology, Loma Linda University, Loma Linda, California, USA *Qinqin Gao, Xiaolin Zhu and Jie Chen equally to this work.
Qinqin
Q
Gao
Xiaolin
X
Zhu
Jie
J
Chen
Caiping
C
Mao
Lubo
L
Zhang
Zhice
Z
Xu
D000328:Adult; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D011225:Pre-Eclampsia / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D055815:Young Adult; D051028:bcl-2-Associated X Protein / Q000235:genetics
C494826:BAX protein, human; C107489:BIRC5 protein, human; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D051357:Cyclin-Dependent Kinase 2; D020169:Caspases