Role of the angiopoietin/Tie system in pregnancy (Review)

Kappou, Dimitra; Sifakis, Stavros; Konstantinidou, Anastasia; Παπαντωνίου, Ν.; Spandidos, Demetrios Α.

doi:10.3892/etm.2015.2280

Cited by 37 publications

(43 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…34 In contrast, other proteins were lower in cases of PTB compared with term controls and included: JAG1, a protein linked with the notch signaling pathway, 35 MMP-2, a metalloproteinase involved in the breakdown of extracellular matrix that has links with tumor progression 36 notch-3, shown to have a role in fetal-maternal communication during implantation and placentation, 37 and, angiopoietin-2, which has a role in the regulation of endothelial cell survival and vascular maturation. 38 We suggest that alterations in levels of these proteins in early pregnancy are potential markers of subsequent PTB.…”

Section: Methodsmentioning

confidence: 86%

The relationship of circulating proteins in early pregnancy with preterm birth

Lynch

Wagner

Deterding

et al. 2016

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

BACKGROUND Preterm birth (PTB) (<37 completed weeks gestation) is a pathological outcome of pregnancy and a major global health problem. Babies born preterm have an elevated risk for long term adverse medical and neurodevelopmental sequelae. Substantial evidence implicates intrauterine infection and/or inflammation in PTB. However, these are often relatively late findings in the process, when PTB is inevitable. Identification of earlier markers of PTB may make successful intervention possible. Although select proteins, notably, those related to the inflammatory pathways, have been associated with PTB, there has been a lack of research into the role of other protein pathways in the development of PTB. The purpose of this study was to investigate, using a previously described biomarker discovery approach, a subset of circulating proteins and their association with PTB focusing on samples from early pregnancy. OBJECTIVES 1) To perform a large-scale biomarker discovery, utilizing an innovative platform to identify proteins associated with preterm birth in plasma taken between 10 and 15 weeks’ gestation and, 2) To determine which protein pathways are most strongly associated with preterm birth. To address these aims we measured 1129 proteins in a plasma sample from early pregnancy using a multiplexed aptamer–based proteomic technology developed in Colorado by SomaLogic. STUDY DESIGN Using a nested case-control approach, we measured proteins at a single time point in early pregnancy in 41 women who subsequently delivered preterm and 88 women who had term uncomplicated deliveries. We measured 1129 proteins using a multiplexed aptamer–based proteomic technology developed by SomaLogic. Logistic regressions and random forests were used to compare protein levels. RESULTS The complement factors B and H and the coagulation factors IX and IX ab were the highest ranking proteins distinguishing cases of preterm birth from term controls. The top 3 pathways associated with preterm birth were the complement cascade, the immune system and the clotting cascade. CONCLUSIONS Using a discovery approach, these data provide further confirmation that there is an association of immune and coagulation–related events in early pregnancy with preterm birth. Thus, plasma protein profiles at 10–15 weeks of gestation are related to the development of preterm birth later in pregnancy.

show abstract

Section: Methodsmentioning

confidence: 86%

The relationship of circulating proteins in early pregnancy with preterm birth

Lynch

Wagner

Deterding

et al. 2016

American Journal of Obstetrics and Gynecology

View full text Add to dashboard Cite

show abstract

“…Reduced levels of VEGF-a and angiopoietin and increased levels of sENG have been associated with poor angiogenesis, defective vascular transformation in deep placentation disorders associated with fetal growth retardation (52,53,(56)(57)(58). VIP was shown to induce VEGF-a expression and enhance angiogenesis in murine ischemia as well as in human prostate and breast cancer cell lines (59)(60)(61).…”

Section: Discussionmentioning

confidence: 99%

Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy outcome in mice

et al. 2018

View full text Add to dashboard Cite

Immune homeostasis maintenance throughout pregnancy is critical for normal fetal development. Trophoblast cells differentiate into an invasive phenotype and contribute to the transformation of maternal arteries and the functional shaping of decidual leukocyte populations. Insufficient trophoblast invasion, inadequate vascular remodeling, and a loss of immunologic homeostasis are associated with pregnancy complications, such as preeclampsia and intrauterine growth restriction. Vasoactive intestinal peptide (VIP) is a pleiotropic neuropeptide synthetized in trophoblasts at the maternal-placental interface. It regulates the function of trophoblast cells and their interaction with decidual leukocytes. By means of a murine model of pregnancy in normal maternal background with VIP-deficient trophoblast cells, here we demonstrate that trophoblast VIP is critical for trophoblast function: VIP gene haploinsufficiency results in lower matrix metalloproteinase 9 expression, and reduced migration and invasion capacities. A reduced number of regulatory T cells at the implantation sites along with a lower expression of proangiogenic and antiinflammatory markers were also observed. Findings detected in the implantation sites at early stages were followed by an abnormal placental structure and lower fetal weight. This effect was overcome by VIP treatment of the early pregnant mice. Our results support the relevance of trophoblast-synthesized VIP as a critical factor in vivo for trophoblast-cell function and immune homeostasis maintenance in mouse pregnancy.-Hauk, V., Vota, D., Gallino, L., Calo, G., Paparini, D., Merech, F., Ochoa, F., Zotta, E., Ramhorst, R., Waschek, J., Leirós, C. P. Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy outcome in mice.

show abstract

“…A remarkable finding in our study was that levels of Ang-1 in newborns were up to a 10-fold higher, specifically in healthy newborns and those with blood culture negative EOS, than in children or adults in earlier studies ( 13 – 17 , 21 , 22 ). Placental levels of Ang-1 and Ang-2 are high during pregnancy and then quickly drop after birth ( 31 , 32 ). Only one earlier study compared both antepartum and postcaesarean maternal samples with neonatal umbilical cord blood samples ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

Low Serum Angiopoietin-1, High Serum Angiopoietin-2, and High Ang-2/Ang-1 Protein Ratio are Associated with Early Onset Sepsis in Surinamese Newborns

Zonneveld

Jongman

Juliana³

et al. 2017

Shock

View full text Add to dashboard Cite

Purpose:Vascular inflammation and leakage in sepsis is mediated by Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2) and their phosphorylation of the endothelial Tie-2 receptor. This study investigates levels of Ang-1 and Ang-2 in newborns to gain insight in the vascular pathophysiology of early onset sepsis (EOS) within 72 h after birth.Methods:A prospective cohort study was performed among 71 Surinamese newborns treated with antibiotics for suspected EOS and 20 control newborns. Newborns with suspected EOS were divided in two groups: blood culture negative and positive EOS. Ang-1 and Ang-2 levels were measured in serum obtained at the start of antibiotic treatment and at re-evaluation after 48 to 72 h.Results:In this cohort 8.5% of newborns had a positive blood culture. At the start of antibiotic treatment Ang-1 serum levels were lower (P < 0.01), and Ang-2 and Ang-2/Ang-1 serum protein ratios were higher (P < 0.01 and P < 0.01, respectively) in newborns with blood culture positive EOS than in controls. These levels were not dependent on timing of first blood draw after birth. After 48 to 72 h levels of Ang-1 further decreased in blood culture positive EOS, while in the other groups no change was observed.Conclusions:Our findings support the hypothesis that a disbalance in the Angiopoietins plays a role in the vascular pathophysiology of EOS.

show abstract

Role of the angiopoietin/Tie system in pregnancy (Review)

Cited by 37 publications

References 65 publications

The relationship of circulating proteins in early pregnancy with preterm birth

The relationship of circulating proteins in early pregnancy with preterm birth

Trophoblast VIP deficiency entails immune homeostasis loss and adverse pregnancy outcome in mice

Low Serum Angiopoietin-1, High Serum Angiopoietin-2, and High Ang-2/Ang-1 Protein Ratio are Associated with Early Onset Sepsis in Surinamese Newborns

Contact Info

Product

Resources

About