晚期和早期发病子痫前期胎盘血管生成增加与血管内皮生长因子受体 2 的差异激活有关。
Increased placental angiogenesis in late and early onset pre-eclampsia is associated with differential activation of vascular endothelial growth factor receptor 2.
机构信息
Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, Universidad del Bío-Bío, Chillán, Chile.
Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Group of Research and Innovation in Vascular Health (GRIVAS Health), Department of Basic Sciences, Universidad del Bío-Bío, Chillán, Chile.
出版信息
Placenta. 2014 Mar;35(3):207-15. doi: 10.1016/j.placenta.2014.01.007. Epub 2014 Jan 29.
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.
简介
早发型（EOPE）和晚发型子痫前期（LOPE）的胎盘都有灌注不足的迹象，而灌注不足反过来又可能与血管生成改变有关。血管内皮生长因子受体 2（VEGFR2）的酪氨酸 951（Y951）和 Y1175 磷酸化是由 VEGF 诱导的，触发了血管生成过程。内皮标记物如 CD31 和 CD34 已被用于估计包括胎盘在内的几种组织中的血管生成过程。我们想知道胎盘绒毛中的血管密度是否与 LOPE 或 EOPE 中 VEGFR2 的 Y951/Y1175 磷酸化有关。
方法
我们从正常妊娠（n = 22）、LOPE（n = 13）、EOPE（n = 15）和早产（n = 10）孕妇的胎盘组织中获取了胎盘样本。使用胎盘组织切片进行 CD31 免疫染色。我们通过 Western blot 和定量 PCR 来估计 CD31、CD34、VEGF 和 VEGFR2 的表达。通过 Western blot 来估计 VEGFR2 的 Y951 磷酸化，而通过 ELISA 来分析 Y1175 磷酸化。
结果
与正常妊娠相比，LOPE 和 EOPE 的终末绒毛中的血管密度以及 CD31 和 CD34 蛋白丰度增加。然而，LOPE 的 CD31 和 CD34 mRNA 水平低于正常妊娠，而 EOPE 的 VEGF mRNA 水平高于正常妊娠。在研究的各组之间，VEGFR2 蛋白浓度没有差异。LOPE 中 VEGFR2 的 Y951 和 Y1175 磷酸化高于正常妊娠组，但仅 EOPE 中的 Y951 与正常妊娠相比表现出更高的磷酸化。
讨论
子痫前期胎盘中血管形成的变化存在争议。我们的研究表明，LOPE 和 EOPE 都存在促血管生成状态。然而，这些变化与内皮标记物的差异表达和 VEGFR2 的激活有关。
结论
有证据表明，LOPE 和 EOPE 中的胎盘血管生成增加，这与 VEGFR2 的差异激活有关。
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