Study On The Role Of VEGF And P53in Normal Pregnancy And Preeclampsia

Background and Objective Preeclampsia (PE) is a pregnancy-specific disease characterized by new-onset hypertension, proteinuria, and edema after20weeks of pregnancy. The global incidence of PE is about5%to8%and the incidence of PE in developing countries is even higher. PE which causes over63000maternal deaths worldwide every year, is a serious threat to the health of mother and child. The exact etiology and pathogenesis of preeclampsia remains unclear. The vascular endothelial dysfunction and the placenta superficial implantation theory are two hot spots of research at present. Previous study showed that VEGF plays an important role in maintaining normal endothelial function. The normal (wild-type) p53protein is encoded by tumor suppressor gene p53. Studies have shown that a large amount of p53protein is produced by the human placenta in abnormal pregnancies and it is accepted that wild-type p53indirectly represses VEGF expression, and thus plays a role in antiangiogenic activity. This conclusion above has been confirmed in the research of tumorigenesis, while the relationship between p53and preeclampsia has not been reported. The research through the detection of the expression changes of VEGF and p53in the placentas of normal late pregnancy and preeclampsia, in order to investigate the role of VEGF and p53in the pathogenesis of preeclampsia, and provide clues for further searching the pathogenesis of preeclampsia.Methods A total of60cases of pregnant women who underwent cesarean section in Qilu Hospital of Shandong University were enrolled in this study. The selected cases were all singleton pregnancies. These cases were divided into PE group which included15patients with mild preeclampsia and20patients with severe preeclampsia and control group which included25cases of normal third trimester pregnant women. Central portions of placentas without bleeding and calcification were collected within10minutes after placental delivery. The size of placental tissue was about1.0cm x1.0cm x1.0cm. The immunohistochemical SP method was used to detect the expression of VEGF and p53in the placenta.Results1. The staining of VEGF was observed both in the placentas of preeclampsia and control group and mainly located in the cytoplasm of cells(syncytiotrophoblast, cytotrophoblast, endothelial cells). The expression of VEGF in the placenta of severe preeclampsia group was significantly lower than that in the control and mild preeclampsia group [IOD:0.0073206(0.0001920-0.0793925) vs.0.0751931(0.0169233-0.1598209),P=0.000;0.0073206(0.0001920-0.0793925) vs.0.0956797(0.0116911-0.1347583),P=0.000]. While the VEGF expression of the mild preeclampsia and normal control group in the placenta had no significant difference[0.0956797(0.0116911-0.1347583) vs.0.0751931(0.0169233-0.1598209), P=0.834]. The expression of VEGF in every group had no significant correlation with gestational age(control group:r=0.103, P=0.625; mild preeclampsia:r=0.321, P=0.244; severe preeclampsia:r=0.077, P=0.747).2. In the placentas of both normotensive and preeclamptic pregnancies, immunostaining showed that p53protein exists in the nucleus of cytotrophoblast cells, syncytiotrophoblast cells and extra-villous trophoblast cells. The expression intensity of p53in the placenta of patients with preeclampsia was significantly increased comparing with normal control group [4(3-5) vs.3(2-5),P=0.027;7(6-7) vs.3(2-5), P=0.000]. The placental expression intensity of p53in the severe preeclampsia group was also significantly higher than that in the mild preeclampsia group [7(6-7) vs.4(3-5), P=0.000]. There was no significant correlation between the expression of p53and gestational age (control group:r=-0.099, P=0.639; mild preeclampsia:r=0.433, P=0.107; severe preeclampsia:r=0.253, P=0.281). 3. The expression of VEGF and p53in placenta was significantly negatively correlated (r=-0.416, P=0.002).Conclusion1. The expression of VEGF in the placenta of severe preeclampsia was significantly lower than that in the normal late pregnancy and mild preeclampsia group, suggesting that VEGF may be involved in the pathogenesis of preeclampsia and associated with the severity of preeclampsia.2. The protein of p53exists in the placentas of both normotensive and preeclamptic pregnancies. The expression of p53in preeclampsia placenta was significantly higher than that in normal, and the more severe the disease, the higher the expression level of p53. This indicates that p53may be involved in the development of preeclampsia.3. The negative correlationship between the expression of VEGF and p53in the placenta confirms that the p53may indirectly repress the expression of VEGF through various means. The low expression of VEGF may further worsen the condition of preeclampsia.