Ultrastructure and histomorphometric analysis of human umbilical cord vessels in preeclampsia: a potential role of VEGF, VEGFR-1 and VEGFR-2

Aim: This study aimed to analyze the ultrastructure and histomorphometric changes of the human umbilical cord vessels of preeclampsia compared to healthy pregnancies and the possible role of vascular endothelial growth factor (VEGF) and its receptors. Materials and Methods: Umbilical cord (UC) specimens were collected between August, 2014 and July, 2015. Histomorphometric analysis of UC vessels was performed utilizing an image analysis system. Cellular localization of VEGF, VEGFR-1 (VEGF receptor-1) and VEGFR-2 (VEGF receptor-2) were examined in immunohistochemically-stained sections of UC from 45 pregnancies with preeclampsia (PE) and 40 healthy pregnancies. Results: Compared with healthy pregnancies, UC venous measurements were significantly higher in PE; total venous area (p<0.001), lumina] venous area (p<0.001) and luminal venous index (p=0.005). Arterial measurements except for the total arterial area were significantly lower in the PE compared to healthy pregnancies, luminal arterial area (p=0.32) and luminal arterial index (p=0.004). Histological and ultrastructural examination of UC from PE revealed discontinuity of vascular endothelium and disorganized edematous widely spaced smooth muscle cells. We demonstrated a significant increase in tissue expression of VEGF in PE (16.6 +/- 0.1) compared to healthy pregnancies (12 +/- 0.8) (p=0.001). Also, significant higher VEGFR-1 expression in PE (20.5 +/- 2.5) compared to healthy pregnancies (9.5 +/- 1.2) (p<0.001) has been observed. However, tissue expression of VEGFR-2 was decreased significantly in PE (10.5 +/- 0.7) compared to healthy pregnancies (13.8 +/- 1.6) (p=0.043). Conclusions: Altered tissue expression of VEGF and its receptors in the UC vessels could play a crucial role in disturbing the UC vascular endothelium, smooth muscles and measurements and this may underlie the existence of preeclampsia.