Alterations Of FABP4Expressions In Serum And Placenta In Preeclampsia

Objective: Preeclampsia(PE) is a pregnancy-induced systemic diseases.Previous studies have shown that: Oxidative stress can be caused by abnormalblood lipid metabolic regulation, the oxidative stress may contribute tovascular endothelial damage, oxidative stress and vascular endothelial injuryare closely related with the onset of preeclampsia. Fatty acid binding protein4(FABP4) is a member of the family of intracellular FABPs, the FABPsuperfamily consists of9highly conserved cytosolic proteins. FABPs arecapable of binding a variety of hydrophobic ligands, such as long-chain fattyacids, eicosanoids, leukotrienes, and prostaglandins. Fatty acid binding protein4(FABP4) plays an important role in maintaining glucose and lipidhomeostasis. FABP4which is first detected in mature adipocyte cells is alsocalled adipocyte-FABP（adipocyte-FABP, AFABP）. It can adjust adipocytedifferentiation and glucolipid metabolism, regulate macrophage cholesterolaccumulation, participate in the formation of atherosclerosis, promote cellproliferation and differentiation, mediate inflammatory reaction, etc. Studiesin non-pregnancy reveal FABP4is closely related with metabolic diseasessuch as type2diabetes, metabolic syndrome, atherosclerosis, insulinresistance (IR) and so on. While preeclampsia is similar with the dyslipidemiain atherosclerosis, has many common features with the metabolic syndrome.Preeclampsia is related with excessive insulin resistance and various kinds offactors and biomarkers of inflammation. This study tested FABP4in serumand placental tissues in patients with preeclampsia, in order to investigate itsrelationship with the pathogenesis of preeclampsia.Methods：From Jun.2011to Sep.2012,56women with preeclampsia whodelivered in The Second Affiliated Hospital of Hebei Medical Universityrecruited in the study, including30women with severe preeclampsia(SPE; group A) and26women with moderate preeclampsia (MPE; group B).25healthy pregnant women were taken as control group (group C). Extraction ofpreeclampsia group (group A and B, before drug treatment) and control groupof pregnant women each6ml peripheral venous blood. Coagulation tube3ml,2000RPM centrifugal10minutes, drain the upper serum in EP tube, placed ina-80℃refrigerator, until the same batch of determination of serum level ofFABP4. Another3ml in coagulation tube for the detection of TG,(triglycerides, TG), CHOL (total cholesterol,CHOL), HDL (high densitylipoprotein, HDL), LDL(low density lipoprotein, LDL), GLU(glucose, GLU)etc. Wthin30minutes ater delivery, placental fragments approximately1cm3in size were sharply dissected at a site midway between the cord insertion andthe lateral placental margin and midway between the chorionic and basalplates.4%formaldehyde fixed24hours for paraffin embedding for HEstaining and immunohistochemistry. The serum level of FABP4was detectedby enzyme-linked immunosorbent assay (ELISA). HDL, LDL, TG, CHOL,biochemical index determination by automatic biochemical detector. Andrecord the blood pressure, height, weight and other indicators. Respectively ineach group take10subjects using immunohistochemical staining method todetect FABP4protein expression in placenta tissues, and applied theImage-pro plus6.0image analysis software to calculates the average opticaldensity value FABP4protein in each group. All the data were analyzed bySPSS13.0software.Results：1The serum levels of FABP4in group A,group B and group C are(9.71±3.94)ng/ml，(7.44±3.35)ng/ml，(5.20±3.82)ng/ml. under pairwisecomparison, all have significant difference (P<0.05，P<0.001，P<0.05).FABP4level of group A [(9.71±3.94) ng/ml]is significantly higher thangroup C[(5.2±3.82) ng/ml], with significant statistical difference(P<0.001).2Among the index of lipid metabolism: Serum TG levels in group A,group B and group C gradually decline, Serum TG level in Group A andgroup B [(4.98±1.75),(3.94±1.25) mmol/L] is significantly higher than group C [(2.41±0.83)mmol/L]. Compared respectively, Differences all havestatistical meaning(P<0.001, P<0.001). Compared group A with group B,difference also have statistical significance (P<0.05). Serum HDL levelsgradually increase in group A、group B and group C. Serum HDL levels inGroup A and group B[(1.4±0.34),(1.64±0.49) mmol/L] lower than group C[(2.41±0.83)mmol/L]. Compared respectively, both have statisticallysignificant(P<0.001，P<0.05). Difference between group A and group B alsohave statistical significance(P<0.05). The serum CHOL of groupA comparedwith group B and group C, difference have statistical significance (P<0.05,P<0.05), group B compared with group C there was no statistically significantdifference (P>0.05). The rest of the various indicators have no significantdifferences between groups.3Serum FABP4concentrations in preeclampsia （group A+group B）correlated positively with TG，CHOL（r=0.928, r=0.46,P<0.05，P<0.05）,andhave no relation with HDL,LDL,GLU, pre-pregnancy BMI(all P>0.05);Serum FABP4concentrations in control group(group C) correlated positivelywith TG, pre-pregnancy BMI （r=0.838,r=0.484，both P<0.05）, and have norelation with HDL,CHOL,LDL,GLU.4HE staining：syncytiotrophoblast of the control group(group C) locatedat the most surface layer of the villus, nuclei are arranged neatly.Cytotrophoblasts are located under the syncytiotrophoblast layer, closelycontact with syncytiotrophoblast cells. Cytotrophoblasts of the preeclampsiagroups are proliferation, syncytiotrophoblasts are shown as aging states,Villous vascular density is bigger, syncytiotrophoblast knots increase.5Immunohistochemical results: FABP4have positive expression in allthe placenta tissues of the three groups. FABP4was detected in the cytoplasmin vascular endothelial cells of the tertiary and some secondary villi, but mostvessels in primary villi vessels are negative. The average OD values of thethree groups are0.12±0.01，0.10±0.02，0.04±0.01, respectively. All havesignificant difference after pairwise comparison (all P<0.05). Furthermore,the average OD values of FABP4in placenta in preeclampsia（group A and group B） correlated positively with the blood FABP4concentrations inpreeclampsia.(r=0.64，P<0.05).Conclusions：1Compared with the control group, serum values of FABP4inpreeclampsia are significantly elevated especially in the severe group. FABP4may play an important role in pathophysiology and relate to the severity of thedisease.2Serum FABP4values are significantly increased in preeclampsia.Furthermore, blood FABP4concentration correlated positively with the serumTG, CHOL values. FABP4may involve in the pathogenesis of preeclampsiaby regulating lipid metabolism.3FABP4immunoreactivity in endotheliocyte is detected mostly in smallvessels in tertiary and some secondary villi, consistent with the transplacentaltransport of lipids from the maternal blood through the syncytiotrophoblastand capillary endothelial cells into the fetal circulation. The expressionpattern of FABP4suggests that it may play a key role in this transportfunction.4Increased FABP4expression in placenta may contribute to high serumFABP4level in women with preeclampsia.