Serum levels of soluble FMS-like tyrosine kinase 1 and endothelial glycocalyx components in early- and late-onset preeclampsia

Introduction: The most popular model of preeclampsia (PE) is a two-stage one in which the first stage involves a decreased perfusion of the placenta and the second stage is characterized by maternal endothelial injury and dysfunction. This model seems to be more appropriate for early-onset PE, than for the late-onset disease, as in the case of the latter the event of reduced placental perfusion seems is less obvious. The aim of the study was to assess the possible correlations between the serum levels of soluble FMS-like tyrosine kinase 1 (sFlt-1) and the components of endothelial glycocalyx (EG), namely syndecan -1 (SDC-1) and hyaluronan (HA), as the markers of endothelial damage, in patients with early- and late-onset PE. Materials and methods: The study was conducted among 60 women in their late second and third trimester of the singleton pregnancy, including 20 patients with early-onset PE, 20 with late-onset PE, and 20 women with normal pregnancy, who served as the control group. All patients were hospitalized between 2015 and 2018 at the Division of Reproduction of Poznan University of Medical Sciences. The women in the control group were matched by gestational age with the patients in the study groups. Results: The median serum level of sFlt-1 was the highest in the patients with early-onset PE (3.53 (2.73-4.5) pg/ml) but it was not statistically different from the level in the patients with late-onset PE (3.14 (2.2-3.4) pg/ml). The mean serum level of SDC-1 also did not differ significantly between the two groups of patients with PE (6.17 +/- 2.2 ng/ml in early-onset PE; 6.42 +/- 2.2 ng/ml in late-onset PE). Both values of SDC-1 were significantly lower than that in the healthy pregnant women (11 +/- 2.62 ng/ml, p < .001). The median concentrations of HA did not differ between patients with early- (236.6 (101.1-351.9) ng/ml) and late-onset PE (234.7 (46.8-324.2) ng/ml). However, the levels in these study groups were significantly higher than in the control group (113.9 (30.9-379.8) ng/ml, p < .001). There was no significant correlation found between the serum concentrations of sFlt-1 and both HA and SDC-1; however, such trend was noticed between the serum concentrations of sFlt-1 and HA in patients with early-onset PE, but not in those with the late-onset disease Conclusions: Evaluation of serum concentrations of HA in patients with PE was found to be more useful in the assessment of endothelial injury, compared to the assessment of SDC-1.The degree of EG damage was comparable in patients with early- and late-onset PE. The pathomechanism of the damage seems to be more sFlt-1 dependent in patients with early- onset PE than in the case of late-onset disease. The two-stage model of PE is more appropriate for early - onset PE, whereas the pathophysiology of the late-onset disease is rather more complex and heterogenous.

Automated summary

Evaluation of serum concentrations of HA in patients with PE was found to be more useful in the assessment of endothelial injury, compared to the assessment of SDC-1. The degree of EG damage was comparable in patients with early- and late-onset PE. The pathomechanism of the damage seems to be more sFlt-1 dependent in patients with early- onset PE than in the case of late-onset disease.