Investigation of the relation of maternal serum endocan levels to preeclampsia presence and severity

Introduction

Preeclampsia (PE) is known to be the common cause of both maternal and fetal mortality and morbidity in pregnancy [1]. It is revealed that the loss of the capacity of remodelling in the spiral arteries of uterus, results in a severe uteroplacental resistance. The vascular resistance decreases the perfusion and impairs the oxygenation of placental and fetal tissues. Placental hypoxia triggers the release of some cytokines like interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) [2]. Due to the fact that maternal vascular disorders affect the growth of the fetus and placenta, investigating the predictors of hypoxia is important as much as its consequences.

Endocan is a soluble proteoglycan that originates specifically from endothelial cells. In the literature, it was shown to be a possible predictor of vascular endothelium related diseases [3], [4]. Endocan is thought to have some non-classical functions during the inflammatory processes which were affected by several cytokines. It was detected that TNF-α and interleukin 1-beta (IL-1b) stimulate the secretion of endocan, whereas interferon-γ inhibits it [5].

The role of angiogenic proteins in early placental vascular development are under investigation because the molecular basis for abnormal placental development and placental dysregulation of these pathogenic factors of PE remains unknown. In this study, we compared the maternal serum endocan concentration between pregnant women with PE and healthy pregnant women to investigate whether the maternal serum endocan levels were correlated with the presence and severity of PE.

Materials and methods

Results

A total of 45 women with the diagnosis of PE and 25 healthy women without PE (matched for age and parity with study group) were included in the study. The characteristics of the groups are shown in Table 1. No significant differences in terms of maternal age (years) and gestational age at admission was found between the groups. Arterial BP was detected higher in PE group than control group (Table 1).

Patients with PE (including both mild and severe PE) had significantly higher maternal serum endocan levels than controls (p=0.002). Edocan levels were also significantly higher both in the mild PE group than control group (p=0.01) and in the severe PE group than control group (0.008) (Figure 1). No significant difference was detected in serum endocan levels between the mild PE group and the severe PE group (p=0.7) (Table 2).

Figure 1:

Endocan concentrations in the different study groups.

Maternal serum endocan level is detected as significant in prediction of preeclampsia according to receiver operating characteristic analysis of the biomarker to identify the patients with PE (AUC: 0.723, p=0.002). Optimal cut-off value was detected as 1234.55 with 70% sensitivity and 60% specificity (Figure 2).

Figure 2:

Receiver operating characteristic analysis of endocan.

Discussion

By researching the maternal serum endocan levels in pregnant women with both mild and severe PE, we intended to find a relation of this marker in presence of PE and also a cut-off value for the disease prediction. In our study we found higher levels of maternal serum endocan in patients with PE. In the lights of our promising results, we suggest that endocan can be used for diagnosis.

Vascular growth of placenta depends on angiogenesis and arterial remodelling [7], [8]. Pathogenesis of PE is known to be based on the dysfunction of endothelium and inflammation [9]. Endocan is thought to induce this inflammation and dysfunction [10]. In vitro experiments showed that TNF-α stimulated the release of endocan [11]. Furthermore, in another study, it was revealed that the pregnant women with PE had higher number of vascular endothelial growth factor receptor (VEGFR) compared to normal ones [12]. VEGF which has an essential role in angiogenesis, is thought to be released by placenta and detected to stimulate the production of endocan [12]. It was proven that a mild inflammatory reaction could be seen in a normotensive healthy pregnant woman which is consistent with our results that endocan levels were increased during normal pregnancy [13]. Depending on these results including ours, endocan seems to take place a major role in the pathophysiology of PE. In pregnancy, endocan is said to play an important role in angiogenesis in the early- and midpregnancy [14]. This brings out the relation of endocan with PE in every trimester of pregnancy. Adekola et al. [15], in consistency with our study, showed that the mean maternal plasma endocan levels were higher in PE compared to uncomplicated pregnancies. In contrast, Yuksel et al. [16] did not detect any significant difference in mean endocan levels between women with PE and women with healthy pregnancies.

In the literature it is clear that the majority of studies of endocan-1 have been in tumours and inflammatory conditions [17], [18], [19]. Distinctively, our study is the first study that assessing the maternal serum endocan level as a biomarker for the presence and especially the severity of PE. In the literature some markers either alone or in combination have been suggested to support the diagnosis of PE [20]. Mendola et al. [21] reported higher retinol binding protein 4 levels in women with PE. Jung et al. [22] investigated urinary and maternal serum nephrine concentrations in PE. Hematocrit and plasma albumin levels were either investigated about this issue [23]. There are lots of other markers investigated for PE prediction and severity [24], [25]. However, they were shown in the case studies of limited populations. In our study, compared to mild PE, we found serum endocan levels higher in severe PE. According to our results we also could not detect any significant difference in serum endocan levels between the mild PE group and the severe PE group. This result reveals that endocan is not a suitable marker for detection of disease severity.

PE often results in induced preterm births which necessitate neonatal intensive care units. They are in limited numbers especially in developing countries like ours and leads to a huge financial problems. So the need of a cost-effective and easily applicable test is clear. By diagnosing the patients before the symptoms occur, physicians can provide better prenatal care for these patients at risk. Although the most beneficial way of detecting PE is the measurement of angiogenic factors (VEGF, PlGF, sFlt-1, sEng) in blood or urine, these tests are not in clinical use yet [26].

Due to the fact that a treatment can be given between the gestation of 12–16 weeks, the best screening test for PE seems to be performed between these weeks. Therefore, our study may guide the researchers to investigate the success of endocan for the detection of PE in a larger sample of pregnant women especially in 12–16 weeks of gestation.

Consequently we revealed that maternal serum endocan levels were increased in pregnant women with PE, so we suggest endocan as a new biomarker for the early diagnosis and estimation of the severity of PE. However, to reach the accurate results, future studies should be set up with extended populations including different subgroups.