Increased placental angiogenesis in late and early onset pre-eclampsia is associated with differential activation of vascular endothelial growth factor receptor 2

• Published in: Placenta (Eastbourne) Vol. 35; no. 3; pp. 207 - 215
• Main Authors: Escudero, C, Celis, C, Saez, T, San Martin, S, Valenzuela, F.J, Aguayo, C, Bertoglia, P, Roberts, J.M, Acurio, J
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-03-2014; Elsevier
• Subjects: Adult; Angiogenesis; Antigens, CD34 - metabolism; Biological and medical sciences; Embryology: invertebrates and vertebrates. Teratology; Female; Fundamental and applied biological sciences. Psychology; Humans; Internal Medicine; Neovascularization, Pathologic - physiopathology; Obstetrics and Gynecology; Phosphorylation; Placenta; Placenta - blood supply; Placenta - metabolism; Platelet Endothelial Cell Adhesion Molecule-1 - metabolism; Pre-eclampsia; Pre-Eclampsia - metabolism; Pregnancy; Premature Birth; RNA, Messenger - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; VEGFR2; VEGFR2; Phosphorylation; tyrosine 951; VEGF; Y1175; Pre-eclampsia; IL-8; late-onset pre-eclampsia; tyrosine 1175; Angiogenesis; Placenta; early-onset pre-eclampsia; Y951; vascular endothelial growth factor; LOPE; vascular endothelial growth factor receptor type 2; EOPE; interleukin 8; Late; Pregnancy disorders; Fetal membrane; Activation; Pregnancy toxemia; Vertebrata; Vascular endothelium growth factor; Mammalia; Preeclampsia; Early; Biological receptor
• ISSN: 0143-4004; 1532-3102
• DOI: 10.1016/j.placenta.2014.01.007

Abstract Introduction Placentas from both early-onset (EOPE) and late-onset pre-eclampsia (LOPE) exhibit signs of underperfusion, which in turn, may be associated with altered angiogenesis. Tyrosine 951 (Y951) and Y1175 phosphorylation of the vascular endothelial growth factor receptor 2 (VEGFR2) induced by VEGF triggers the angiogenesis process. Endothelial markers such as CD31 and CD34 have been used for estimating angiogenic processes in several tissues, including placenta. We asked whether vascular density in placental villi was related to Y951/Y1175 phosphorylation of VEGFR2 in LOPE or EOPE. Methods We obtained placental samples from women with normal pregnancies ( n  = 22), LOPE ( n  = 13), EOPE ( n  = 15) and preterm deliveries ( n  = 10). Slices from placental tissue were used for CD31 immunostaining. We estimated the expression of CD31, CD34, VEGF, and VEGFR2 by western blot and quantitative PCR. Y951 phosphorylation of VEGFR2 was estimated by western blot, whereas Y1175 phosphorylation was analyzed by ELISA. Results Vessel density in terminal villi and CD31 and CD34 protein abundance were increased in LOPE and EOPE compared to normal pregnancy. However, mRNA levels for CD31 and CD34 were lower in LOPE than in normal pregnancy and VEGF mRNA was higher in EOPE. VEGFR2 protein concentration was not different among the studied groups. Y951 and Y1175 phosphorylation of VEGFR2 was higher in LOPE than in the normotensive group, but only Y951 exhibited greater phosphorylation in EOPE compared to normal pregnancy. Discussion Changes in vessel formation in the pre-eclamptic placenta are controversial. Our study suggests a pro-angiogenic state in both LOPE and EOPE. These changes are however, associated with differential expression of endothelial markers and VEGFR2 activation. Conclusion There is evidence of increased placental angiogenesis in LOPE and EOPE that is associated with differential activation of VEGFR2.