The Relationship Of Angiopoietin-related Growth Factor With Pregnancy And Preeclampsia

Background:Pregnancy is the maturation process of the embryo/fetus in uterus and is the fundamental of human procreation. Pregnancy not only relates to the family and social harmony and stability, but also relates to the prosperity of national. Normal pregnancy and a good outcome is not only assurance for the health of offspring and national quality, but also save health care resources and bring happiness and joy for people. Pregnancy is complex, precise and mysterious. Pregnancy involves the reproductive system, respiratory system, circulatory system, endocrine system, immune system and metabolism and all of them have a series of physiological changes during pregnancy. However, our knowledge about the process of natural pregnancy is limited in many aspects. The limitations of pregnancy biological understanding have prevented scholars exploring the etiology and pathophysiology, further improvement of efficacy, the prediction and prevention on preeclampsia, miscarriage and other pregnancy complications, and so on.Preeclampsia complicates 7-12% of all pregnancies worldwide and is a pregnancy-specific disease which serious impacts on maternal and children's health and is a major cause of maternal, fetal and neonatal mortality. The main pathological changes of preeclampsia is systemic small artery spasm, vascular endothelial cell damage, coagulation system activation, and all of them result in the performance of maternal hypertension, proteinuria, edema, and severe preeclampsia can lead to the appearance of seizures (eclampsia) and even maternal death; and in the fetus, preeclampsia can lead to the appearance of restriction of fetal growth, fetal distress,and/or even fetal death. Therefore, it is important to explore the pathogenesis of preeclampsia for the preeclampsia prevention and treatment to reducing maternal, fetal and neonatal mortality in the perinatal period.Diagnosis and treatment of preeclampsia has made significant progress. In recent years, because of increasing efficacy and prognosis improved significantly, even early onset and severe preeclampsia after appropriate treatment can also achieve good outcomes. However, the exact etiopathogenisis of preeclampsia is unknown. And it is not yet possible to predict the occurrence of preeclampsia and it is not yet possible to take the appropriate measures to prevent the appearance of preeclampsia. Can not predict and prevent preeclampsia has been the bottleneck to improve the prognosis of preeclampsia. It is important to clarify the etiology and pathogenesis of preeclampsia and to offer the potential strategies for disease prediction and prevention and to improve the efficacy and prognosis furthermore.Shallow placental implantation, abnormal recast of spiral arteries, angiogenesis disorders, and systemic vascular endothelial cell damage is the core of the pathophysiology in preeclampsia. Recently liver-derived angiopoietin-related growth factor (AGF, also known as Angptl6) has been introduced as a novel circulating protein which has the function to promote angiogenesis as confirmed, but the research about preeclampsia and the AGF is still rare.Objectives:To observe the serum AGF levels in the normal non-pregnant women,normal pregnant women of first trimester, second trimester,third trimester,and 1,3,days after cesarean of normal pregnant women.To observe the serum AGF levels in preeclampsia patients and normal pregnant women of third trimester with whose age,gestational age matched.To observe the expression of AGF mRNA and protein in placenta of preeclampsia and normal pregnant women.Then to clarify the circulating AGF variation in normal pregnant women and in preeclampsia patients, to clarify the relationship between the AGF expression of placenta and preeclampsia,and then to explore the changes and meaning of AGF in normal pregnancy,to explore the role of AGF in the occurrence and the development of preeclampsia.Methods:Our investigation included three parts.The first part included thirty normal non-pregnant women,thirty normal pregnant women of first trimester,thirty normal pregnant women of second trimester,fifty-eight normal pregnant women of third trimester,and fifteen of normal pregnant women of third trimester with 1,3,days after cesarean. Enzyme linked immunosorbent assay was employed to detect AGF levels in serum.The second part included forty-six preeclamptic patients (eight severe preeclamptic patients with fetal growth restriction (FGR)) and fifty-eight normal pregnant women who were the same as the first part and all of them had caesarean section to stop pregnancy. Enzyme linked immunosorbent assay was employed to detect serum AGF levels. The third part included thirty-six preeclamptic patients and thirty-six normal pregnant women.Real-time fluorescence quantitative PCR was employed to detect placental mRNA expression of AGF.Results:The circulating AGF concentrations were significantly higher in normal pregnant women of first trimester, second trimester,third trimester as compared to the normal non-pregnant women(P<0.001). The cycle AGF level of first trimester was the highest and was significantly higher than normal non-pregnant women and normal pregnant women of second trimester (P=<0.001, P=0.033, respectively), but between the normal pregnant women of first, third trimester groups and between the normal pregnant women of second,third trimester groups there was no difference in serum AGF levels (P> 0.05,both and). And the AGF serum concentrations decreased after cesarean, and it was significantly lower in 24 hours and 48 hours postpartum than that of antepartum (P=0.021 and P=0.009, respectively), but there was no significant difference between the 24 hours and 48 hours postpartum (P=0.801).And there was no significant difference in serum AGF levels between the preeclamptic patients and normal pregnant women (P=0.285), and it was the same result between severe preeclampsia groups accompanied and not accompanied with FGR (P=0.41).But it was lower in the placenta expression of AGF mRNA in preeclamptic patients than that of normal,late pregnant women, and the difference was significant (P=0.037).Conclusion1. Circulating AGF levels increased significantly in the normal pregnancy as compared to the normal non-pregnant women, and decreased significantly after delivery, suggesting that during pregnancy placenta is one of the sources of circulating AGF; 2.The expression of placental AGF mRNA was significantly lower in preeclamptic patients than that of normal pregnant control, suggesting that AGF may be associated with the pathogenesis of preeclampsia.