Angiopoietin-1 and Angiopoietin-2 Activate Trophoblast Tie-2 to Promote Growth and Migration during Placental Development

Dunk, Caroline; Shams, M.; Nijjar, Sarbjit; Rhaman, M.; Qiu, Yan; Bussolati, Benedetta; Ahmed, Asif

doi:10.1016/s0002-9440(10)65089-4

Cited by 165 publications

(138 citation statements)

References 30 publications

(58 reference statements)

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“…Doppler velocimetry measures of the umbilical artery support the concept of increased placental vascular resistance [46], similar to what has been reported for early-onset severe FGR in humans [25,26,28]. Furthermore, similar as to what has been reported for term human FGR pregnancies [36,37], fetal cotyledon VEGF, VEGF-R1 Ang 2, and Tie 2 expression is reduced in our near-term sheep FGR pregnancies [45,47]. By contrast, at day 55 p.c.…”

Section: Placental Development In Compromised Pregnanciessupporting

confidence: 88%

“…Greater expression of Ang 2 during the first trimester, with Ang 1 and VEGF expression increasing from early to late gestation [35], fits with the concept that branching angiogenesis occurs during early placental development, followed by nonbranching angiogenesis [29]. The altered placental morphology (i.e., long straight terminal villi) associated early-onset severe FGR may result from increased non-branching angiogenesis, as both VEGF and Ang 2 are reduced in term placenta from this type of pregnancy [36,37], consistent with reduced branching angiogenesis during late gestation.…”

Section: Placental Development In Compromised Pregnanciessupporting

confidence: 65%

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The pregnant sheep as a model for human pregnancy

2008

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Successful outcome of human pregnancy not only impacts the quality of infant life and well-being, but considerable evidence now suggests that what happens during fetal development may well impact health and well-being into adulthood. Consequently, a thorough understanding of the developmental events that occur between conception and delivery is needed. For obvious ethical reasons, many of the questions remaining about the progression of human pregnancy can not be answered directly, necessitating the use of appropriate animal models. A variety of animal models exist for the study of both normal and compromised pregnancies, including laboratory rodents, non-human primates and domestic ruminants. While all of these animal models have merit, most suffer from the inability to repetitively sample from both the maternal and fetal side of the placenta, limiting their usefulness in the study of placental or fetal physiology under non-stressed in vivo conditions. No animal model truly recapitulates human pregnancy, yet the pregnant sheep has been used extensively to investigate maternal-fetal interactions. This is due in part to the ability to surgically place and maintain catheters in both the maternal and fetal vasculature, allowing repeated sampling from non-anesthetized pregnancies. Considerable insight has been gained on placental oxygen and nutrient transfer and utilization from use of pregnant sheep. These findings were often confirmed in human pregnancies once appropriate technologies became available. The purpose of this review is to provide an overview of human and sheep pregnancy, with emphasis placed on placental development and function as an organ of nutrient transfer.

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Section: Placental Development In Compromised Pregnanciessupporting

confidence: 88%

Section: Placental Development In Compromised Pregnanciessupporting

confidence: 65%

The pregnant sheep as a model for human pregnancy

2008

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“…As in baboons of the present study, Ang-1 assessed by in situ hybridization was expressed in high level within the cytotrophoblast and syncytiotrophoblast of the human placenta, where expression also was decreased in late gestation [20]. Also, as shown in baboons, Ang-2 assessed by laser densitometric analysis and immunocytochemistry was localized within villous trophoblast and perivascular tissue of the human placenta [20][21][22][23], where levels showed only a small increase with advancing gestation [20]. In contrast, Ang-2 mRNA levels determined by PCR and Northern blot analysis in whole villous tissue decreased with advancing human [22] and marmoset [24] gestation.…”

Section: Discussionsupporting

confidence: 76%

Differential Expression of Placental Villous Angiopoietin-1 and -2 During Early, Mid and Late Baboon Pregnancy

et al. 2007

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Although vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 have important roles in angiogenesis, very little is known about the regulation of these factors in the villous placenta during human pregnancy. In the present study, to investigate whether placental expression of Ang-1, Ang-2 and VEGF was altered in a cell-specific manner with advancing baboon gestation, the mRNA levels of these growth factors were determined by RT-PCR in cells isolated by Percoll gradient centrifugation from and protein localization assessed by immunocytochemistry in the villous placenta at early (day 60), mid (day 100) and late (day 170, term is 184 days) baboon gestation. Mean (± SE) Ang-1 mRNA levels, relative to 18S rRNA, in villous syncytiotrophoblast (3.92 ± 0.68) and cytotrophoblast (1.31 ± 0.31) cell fractions were highest on day 60 of gestation, then decreased by approximately 2.5-fold (P<0.05) to 1.39 ± 0.29 and 0.49 ±0.07, respectively, on day 170. Moreover, Ang-1 mRNA levels in the villous stromal cells and Ang-2 mRNA levels in all placental villous cell fractions were similar on days 60, 100, and 170 of gestation. In contrast to Ang-1 and Ang-2, placental villous cytotrophoblast VEGF mRNA levels were increased 2.94 fold (P<0.05) between mid (0.67 ± 0.15) and late (1.97 ± 0.49) gestation. A corresponding decrease in Ang-1, absence of change in Ang-2, and increase in VEGF protein immunocytochemical expression were exhibited in placental trophoblast with advancing baboon pregnancy. Ang-1/-2 and the angiopoietin Tie-2 receptor were expressed in vascular endothelial cells of the villous placenta, indicating that these blood vessel cells are a major site of ligand-receptor interaction for angiogenesis during primate pregnancy. We conclude that there is a cell-specific differential change in placental villous trophoblast expression of VEGF, Ang-1, and Ang-2 which we propose is important in regulating angiogenesis in the villous placenta during primate pregnancy.

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“…In vitro experiments have shown that Ang1 has speci®c e ects on endothelial cells: it potently induces chemotactic response (Witzenbichler et al, 1998), network formation , sprouting (Koblizek et al, 1998;Kim et al, 1999) and survival in apoptosis Kim et al, 2000a). Although a recent report indicates that Ang2 (250 ng/ml) stimulates proliferation, migration, and release of nitric oxide in trophoblast cells that are expressing the Tie2 receptor (Dunk et al, 2000), the role of Ang2 on cultured endothelial cells is not known.…”

mentioning

confidence: 99%