Maternal, Fetal, and Placental Selectins in Women With Pre-eclampsia; Association With the Renin-Angiotensin-System

Abstract

Selectins [endothelial (E), platelet (P), and leucocytes (L)] are a class of cell adhesion molecules, stimulated in response to inflammation. Pre-eclampsia is characterized by inflammation, and angiotensin II is pro-inflammatory. We hypothesized that circulating maternal and fetal concentrations and placental expression of selectins would be increased in women with pre-eclampsia and would be associated with the angiotensin receptors (AT1R and AT2R). Maternal and fetal blood and placental tissue was collected at delivery from White European normotensive controls (n = 17) and women with pre-eclampsia (n = 17). Soluble (s) E-, P- and L-selectin protein concentrations were measured by ELISA and placental protein expression was examined by immunohistochemistry. Maternal sE-selectin concentrations were increased in pre-eclampsia (P < 0.001); conversely fetal sE- and sP-selectin levels were lower in pre-eclampsia (P < 0.05 for both). Staining was mainly localized to the syncytiotrophoblast for all selectins. E-selectin expression was increased, while P-selectin was decreased in placental from pre-eclampsia (P < 0.05 for both); no differences were observed for L-selectin expression. Both E- and L-selectin were positively correlated (P < 0.008; P < 0.02) with AT2R placental expression, whilst P-selectin was negatively associated with AT1R (P < 0.005), all only in the pre-eclampsia group. This novel study reports maternal, fetal and placental expression of selectins in pre-eclampsia. The increased E-selectins reflect the endothelial dysfunction, characteristic of pre-eclampsia. In contrast, the reduced P-selectins and the positive association of placental AT2Rs with both E-and L-selectin in pre-eclampsia could be a protective mechanism to limit the endothelial dysfunction.

Keywords: angiotensin receptors; endothelial dysfunction; inflammation; pre-eclampsia; selectins.

Figure 1

Maternal and fetal soluble (s) (A) E-selectin; (B) P-selection and (C) L-selectin concentrations between normotensive control (NC) and pre-eclamptic (PE) pregnancies. (D) Maternal sE-selectin concentrations when sub-grouped by NC, early-onset PE (diagnosis ≤ 34 weeks gestation; n = 6) and late-onset PE (>34 weeks gestation; n = 11). Data presented as median [IQR]; *P < 0.05; ***P < 0.0001.

Figure 2

Maternal:fetal ratios of soluble (s) (A) E-selectin; (B) P-selection and (C) L-selectin concentrations between normotensive control (NC) and pre-eclamptic (PE) pregnancies. Data in all box plots are presented as median [interquartile ranges]; **P < 0.001.

Figure 3

Localisation and quantification of placental (A) E-selectin; (B) P-selectin and (C) L-selectin in placenta from normotensive controls (NC (A1, B1, & C1); n = 17) and pre-eclampsia (PE (A2, B2, & C2); n = 17). Negative controls for each selectins are shown in A3, B3, & C3 respectively. In photomicrographs, positive cells appear in brown; magnification x400. Scale bars represent 100 μm. Protein expression was localized to the syncytiotrophoblast layer (black arrows) and some fetal vessels (red arrows). (D) E-selectin; (E) P-selectin and (F) L-selectin expression in placenta, when sub-grouped by NC, early-onset PE (diagnosis ≤ 34 weeks gestation; n = 6) and late-onset PE (>34 weeks gestation; n = 11). Data in all box plots are presented as median [interquartile ranges]; *P < 0.05; **P < 0.001.

Figure 4

Scatter plots illustrating the positive relationship between (A) placental E-selectin (r = 0.55; P = 0.008) and (B) L-selectin (r = 0.61; P = 0.02) with angiotensin type 2 receptor (AT2R) and (C) the negative association between placental P-selectin (r = 0.68; P = 0.005) with angiotensin type 1 receptor (AT1R).