Expression of mammalian target of rapamycin (mTOR), nuclear factor-κ B (NF-κB) and sterol regulatory element binding protein 2 (SREBP2) in serum and placentas among gravidas with preeclampsia

Abstract

Objective To investigate the level of mammalian target of rapamycin (mTOR) in serum and the expression of mTOR, nuclear factor-κ B (NF-κB) and sterol regulatory element binding protein 2 (SREBP2) in placenta among gravidas with preeclampsia. Methods From August 2015 to August 2017, 60 gravidas including 40 with severe preeclampsia (SPE) and 20 with mild preeclampsia (MPE) who underwent regular prenatal care and delivered by caesarean section were selected from the Second Xiangya Hospital of Central South University. According to the ratio of 2∶1, 30 gravidas who delivered through caesarean section due to cephalopelvic disproportion, abnormal fetal position or social factors during the same period were enrolled as the control group. Peripheral blood samples were obtained to determine the concentrations of serum mTOR, high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglyceride (TG) and total cholesterol (TC) by enzyme linked immunosorbent assay (ELISA). The expression of mTOR, phospho-mTOR (p-mTOR), NF-κB and SREBP2 in placenta were measured by Western blot. Clinical datas were statistically analyzed using one-way ANOVA, Bonferroni or Dunnett's T3 test, and Pearson's correlation analysis. Results (1) The serum levels of mTOR and LDL-C in the SPE and MPE group were both higher than that in the control group [mTOR:(11 765.56±1 698.95) and (8 278.56±1 106.59) vs (4 366.19±716.43) pg/ml; LDL-C:(7.81±1.90) and (4.11±0.75) vs (2.42±0.45) mmol/L, all P<0.05].Furthermore the serum levels of mTOR and LDL-C in the SPE group were both higher than those in the MPE group (both P<0.05). The serum level of HDL-C in the SPE and MPE group were lower than that in the control group [(0.36±0.12) and (0.85±0.11) vs (1.33±0.16) mmol/L, both P<0.05], and that in the SPE group was lower than that in the MPE group (P<0.05). Women in the SPE group showed higher TG level when comparing with the MPE and control group [(46.19±18.92) vs (35.55±6.54) and (33.24±9.78) nmol/L, both P<0.05], while the TC levels in the SPE and MPE group were higher than that in the control group[(24.72±7.17) and (21.83±4.19) vs (16.32±3.88) nmol/L, both P<0.05]. (2) The placental expressions of mTOR, p-mTOR, NF-κB and SREBP2 protein in the SPE and MPE group were higher compared with that in the control group [mTOR: (0.52±0.09) and (0.38±0.08) vs (0.24±0.05); p-mTOR: (0.42±0.08) and (0.26±0.05) vs (0.14±0.03); NF-κB: (0.58±0.10) and (0.36±0.05) vs (0.21±0.03); SREBP2: (0.52±0.08) and (0.33±0.05) vs (0.20±0.05); all P<0.05], and those expressions of the SPE group also higher comparing with the MPE group. Otherwise the p-mTOR/mTOR ratios in the SPE group and MPE group were higher than that in the control group [(0.75±0.10) and (0.69±0.14) vs (0.59±0.13), both P<0.05]. (3) Pearson's correlation analysis showed that serum level of mTOR and placental expressions of mTOR and p-mTOR in the SPE group were positively correlated with serum LDL-C (r=0.682, 0.584 and 0.504, all P<0.05), TG (r=0.612, 0.658 and 0.422, all P<0.05) , while serum level of mTOR and placental expressions of mTOR in the SPE group were positively correlated with TC (r=0.598 and 0.452, all P<0.05), but were negatively correlated with serum HDL-C (r=-0.375, -0.442 and -0.390, all P<0.05). The NF-κB expression in placenta of the SPE group was significantly positively correlated with the mTOR expression in placenta and serum LDL-C (r=0.375 and 0.391, both P<0.05). Moreover, in the SPE group, the SREBP2 level in placenta was significantly positively correlated with placental expression of mTOR and serum TC level (r=0.364 and 0.392, both P<0.05). (4) In the MPE group, mTOR level in serum and levels of mTOR and p-mTOR in placenta were significantly positively correlated with serum LDL-C (r=0.813, 0.641 and 0.465, all P<0.05), TG (r=0.646, 0.529 and 0.502, all P<0.05) and TC (r=0.558, 0.482 and 0.483, all P<0.05), while the level of serum mTOR was negatively correlated with the level of serum HDL-C (r=-0.606, P<0.05). The NF-κB level in placenta in MPE group was positively correlated with the mTOR in placenta and the serum LDL-C (r=0.458 and 0.595, both P<0.05), while the SREBP2 level in placenta was significantly positively correlated with mTOR in placenta and serum TC (r=0.580, 0.560, respectively; both P<0.05) in the MPE group. Conclusions mTOR, NF-κB and SREBP2 may play important roles in the onset and development of preeclampsia by interfering lipid metabolism. Key words: Pre-eclampsia; Mammalian torget of rapamycin; Nuclear factor-κB; Sterol regulatory element binding protein 2