Angiogenesis In Human Placenta Research Articles

Hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway.

Placentation, which is critical for maternal-fetal exchange of nutrients and gases, is a complicated process comprising stepwise vasculogenesis and angiogenesis. Hypoxia caused by impaired trophoblast invasion may cause various angiogenic abnormalities in human placenta. The Notch1 signaling pathway plays an important role in the regulation of angiogenesis. The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notch1/Dell4/Jagged1 were investigated in this study. The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay, so as to discover the possible role of notch1 signaling pathway in the angiogenesis of human placenta. The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions. The mRNA and protein levels of Notch1/Dell4/Jagged1 were decreased in the hypoxic group compared to the control one. In addition, the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition, but promoted when treated with JAG-1. The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch1 signaling pathway.

CCM2 and CCM3 proteins contribute to vasculogenesis and angiogenesis in human placenta

Placenta as an ideal model to study angiogenic mechanisms have been established in previous studies. There are two processes, vasculogenesis and angiogenesis, involved in blood vessel formation during placental development. Therefore, blood vessel formation is a crucial issue that might cause vascular malformations. One of the vascular malformations is cerebral cavernous malformation (CCM) in the central nervous system, consisting of endothelium-lined vascular channels without intervening normal brain parenchyma. Three CCM loci have been mapped as Ccm1, Ccm2, Ccm3 genes in CCM. In order to investigate whether CCM proteins participate in blood vessel formation, we report here the expression patterns of CCM2 and CCM3 in developing and term human placenta by means of immunohistochemistry and Western blot analysis. CCM2 and CCM3 were obviously detected in the vascular endothelium during early pregnancy. Moreover, vascular endothelium of stem villi revealed a moderate immunostaining for CCM2 and, to a lesser extent, in the endothelium of mature intermediate villi in term placenta. Interestingly, CCM3 immuno-staining was weakly localized in the endothelium of mature intermediate villi and showed lesser expression going toward stem villi in term placenta. The expression patterns of the proteins were clearly identified in the vascular endothelium of human placenta, suggesting that they might play roles during angiogenesis and vasculogenesis. Furthermore, with this study, CCM2 and CCM3 have been described for the first time in the human placenta.

The Distribution of Angiopoietin-1, Angiopoietin-2 and Their Receptors Tie-1 and Tie-2 in the Very Early Human Placenta

Angiopoietins are integral to vasculogenesis and angiogenesis, which play crucial roles in the growth and development of the placenta. The current study assessed expression of angiopoietins (Ang-1 and Ang-2) and their receptors (Tie-1 and Tie-2) during development of the early human placenta. First-trimester placental tissues were obtained from women undergoing curettage during normal pregnancies. The use of immunohistochemistry (IHC) showed that Ang-1 was primarily localized to syncytiotrophoblasts where it displayed moderate immunoreactivity, whereas weak immunoreactivity for Ang-1 was observed in endothelial cells and angiogenic cell cords (ACC). Strong immunoreactivity for Ang-2 was also found predominantly in syncytiotrophoblasts with lower immunostaining levels evident in cytotrophoblasts. Moderate immunoreactivity for Ang-2 was observed in endothelial cells, ACC and Hofbauer cells. By contrast, the trophoblastic shell, as well as endothelial cells and ACC exhibited strong staining intensity for Tie-1 with the strongest immunoreactivity for Tie-2 observed in cytotrophoblasts, ACC and endothelial cells. Western blotting of tissue extracts confirmed the IHC results. Previous studies focused on VEGF and its receptors in controlling vasculogenesis and angiogenesis in human placenta. However, the specific localization patterns of angiopoietins and their receptors revealed by the current study emphasize the importance of these molecules in placental vascular development. Functional studies aimed at identifying the molecular mechanisms of actions of these factors and receptors may prove essential in elucidating the pathophysiology of placental disorders such as intrauterine growth restriction and pre-eclampsia.