ABSTRACT
Objective:To search for circulating complement-related proteins that predict hypertensive disorders of pregnancy (HDP) based on reports of the development of gestational hypertension and proteinuria and to investigate the role of the complement system in the development of HDP.Methods:A nested case-control study was used, the serum samples of pregnant women who had been given birth or cesarean section in Guangzhou Women and Children′s Medical Center from November 2014 to March 2017 were collected. A total of 60 HDP and 60 normal pregnant women were included and matched 1∶1 by age and gestational week. Unlabeled mass spectrometry was used to screen the differential expression of complement factors in serum samples of 12 pairs of HDP patients and normal pregnancy collected before 20 weeks of pregnancy, and another 48 pairs of serum samples of HDP patients and normal pregnant women were used for preliminary verification. It was selected when the fold change (FC) of complement factor expression was>1.2 or <0.8 and P<0.05. ROC curve was used to evaluate the diagnostic value of corresponding factors. Results:FC of serum C1s, C8 beta chain (C8β) and C1 inhibitor (C1-INH) of HDP patients were 1.19, 1.23, 0.73 ( t=2.07, 2.06, -3.40; P<0.05), respectively. FC of serum C1s, C8 β, C1-INH, factor H-related protein 5 (CFHR5), clusterin (CLU), and C-reactive protein (CRP) of PE patients were 1.39, 1.50, 0.72, 2.49,4.38, and 1.82 respectively ( t=4.36, 5.61, -3.70, 6.82, 8.70, 7.27; P<0.05).The AUC of combining C1s, C8 β and C1-INH was 0.89 in HDP. The AUC of CFHR5, CLU, and CRP in preeclampsia was 0.88, 0.92, and 0.91. Conclusions:Before HDP, the activation and regulation of classic complement pathway and alternative pathway were disordered in pregnant women. The combined detection of complement C1s, C8 β and C1-INH is expected to be used in the prediction of HDP, and CFHR5, CLU, and CRP are expected to be used in the prediction of preeclampsia.
ABSTRACT
Objective Find abnormal changes of plasma lipid metabolism-related proteins before 20 weeks of gestation in patients with hypertensive disorder of pregnancy(HDP), and preliminarily investigate the role of plasma apolipoprotein C4 elevation in HDP. Methods A nested case-control study was used. The plasma were collected from pregnant women who underwent routine prenatal examination in Guangzhou Women and Children's Medical Center from November 2014 to March 2017. Label-free mass spectrometry was used to detect the differences in plasma lipid metabolism-related proteins before 20 weeks of gestation between 12 pairs of HDP patients and normal controls, and different 48 pairs of samples were used for verification. The protein with the most significant difference multiples was screened to study its effects on monolayer permeability and nitric oxide secretion of endothelial cells. One-way ANOVA was used for comparison between groups, and P<0.05 was considered as statistically significant difference. Results Compared with the control, the lipid metabolism-related proteins, APOC4, Fatty acid-binding protein 4 (FABP4), Apolipoprotein E (APOE), Apolipoprotein C3 (APOC3) and Beta-2-glycoprotein 1(APOH) raised to 1.94, 1.82, 1.59, 1.55 and 1.38 times, phospholipid transfer protein (PLTP) decreased to 0.78 times in plasma before 20 weeks of pregnancy of patients with HDP (t value were 2.499, 2.497, 2.081, 2.098, 2.426 and 2.564, respectively, P<0.05). Cell experiments results showed that 50 ng / ml APOC4 significantly increased 20％ HUVEC single layer cell permeability to FITC-labeled dextran (F=455.4, P<0.01), and significantly decreased the level of nitric oxide in the supernatant of HUVEC culture by 25％ (F=61.92, P<0.01). Conclusions Before diagnosis, plasma protein levels involved in lipid metabolism in HDP patients have been changed, resulting in abnormal lipid metabolism. APOC4 can increase the permeability of vascular endothelial cells, inhibit endothelial source of NO secretion, cause endothelial dysfunction.