The High Levels Of Vitronectin Expressive Profiles In Maternal-fetal Interface Of Patients With Early-onset Severe Preeclampsia And Significance

Preeclampsia（PE） is the most common pregnancy-specific disease that usually occursafter20weeks of gestation. It is defined as new onset of blood pressure≥140/90mmHg withthe proteinuria≥300mg/24h, which may be associated with symptoms such as upperabdominal discomfort, headache, and blurred vision. Preeclampsia is classified into mild andsevere types, depending on the severity of woman’s blood pressure and proteinuria. Thesevere pre-eclampsia is characterized by a further increase in blood pressure that isassociated with massive proteinuria and more severe complications. Early onset severepreeclampsia (EOSP) refers to severe pre-eclampsia before34weeks, followed closely formaternal and perinatal complications. The aetiology of these diseases remain enigmatic andnow it is widely believed that it has been coupled with the changes in pathophysiology ofplacental, resulting in relative placental ischemia and hypoxia, vascular permeability, and theactivation of the coagulation cascade. Vitronectin (VN), a member of adhesion proteinsfamily, has physiological functions such as cell adhesion, regulation of fibrinolysis,coagulation, and immune defense, which may play an imperative role in the occurrence andprogression of severe preeclampsia, especially in EOSP. Through the detection of VNexpression in placentas and coagulation parameters changes in severe preeclampsia(early-onset type and late-onset type), the present study was designed to explore the role andsignificance of VN in the EOSP, providing a theoretical basis of EOSP pathogenesis researchand treatment.Materials and Methods:Samples of maternal-fetal interface placental tissues (infarct center, infarct edge, nearinfarct tissues and away from infarct tissues, or randomly selected non-infarcted placentaltissue) and plasma of early-onset severe preeclampsia, late-onset severe preeclampsia andtwo groups corresponding to the control group were collected. Immunohistochemistry,immunofluorescence, and western blot were used to detect VN protein expression inplacenta, and the level of mRNA expression of VN was detected by RT-PCR. VN’s impacton coagulation were investigated by comparing the differences of prothrombin time (PT), partial thromboplastin time (APTT), fibrinogen (FIB) and thrombin time internationalnormalized ratio (INR) in maternal blood.Results:1. VN’s location in placenta: VN mostly stained in necrosis and fiber ingredients of placentalinfarct area, the intermediate trophoblast cells was strongly expressed around infarctions,which mainly expressed in the cytoplasm, even can be observed in the cell membrane ornucleus.2. VN protein expression levels of placentas in each group: a random high magnificationobservation of the five fields of vision found that, the expression level of VN in theplacentas of EOSP group was the highest, followed by late-onset severe preeclampsia, latein the control group, early in the control group. Each group difference was statisticallysignificant (P <0.001).3. The VN protein expression in the placenta infarct region of the gradient: the VN in theinfarct center, infarct edge, near infarct tiusses and away from the infarct organizations inthe expression level of descending order, the difference was statistically significant (P <0.001). The differences of VN protein expression in the infarct center, infarct edge, near theinfarct organizations and away from the infarct organizations between the groups were notstatistically significant.4. The immunohistochemical results of present study were consistent withimmunofluorescence and Western blotting.5. The VN mRNA expression levels in placentas of EOSP and early control group: the VNmRNA expression has been detected in the infarct center, infarct edge, near the infarcttissue and away from the infarct tissues of both two groups.6. Coagulation parameters determination in maternal plasma of each group: compared withother groups, the PT was significantly shorter in EOSP group, the differences werestatistically significance (p <0.05). The differences of APTT and the INR in each groupwere not statistically significant.7. There was a significant negative correlation between the plasma PT and expression levelsof VN in maternal-fetal interface placental tissues of EOSP (r=0.612, P<0.05)Conclusions:1. High VN expression in the maternal-fetal interface of EOSP group, followed by late-onsetsevere preeclampsia group, suggesting that VN expression is associated with the onsettime of the disease. 2. The VN protein in infarct center may be derived from necrotic trophoblasts.3. The extravillous trophoblasts (EVTs) in maternal-fetal interface placenta tissue in whichVN is highly expressed may secrete the VN.4. VN may play an important role in the repairment of the maternal-fetal interface placentainfarction and coagulation.5. The free VN of the maternal-fetal interface placenta may enter the maternal circulation,which may be one of the reasons of the activation of extrinsic coagulation system andthe imbalance of coagulation and fibrinolysis system.