Soluble endoglin in the pathogenesis of preeclampsia: investigation of mechanisms and the development of therapeutics
Grant number: 1048707 | Funding period: 2013 - 2015
Preeclampsia is a severe disease of pregnancy. As the pathogenesis is poorly understood, the only treatment is for clinicians to deliver babies irrespective of gestation. We have identified MMP-14 as the molecular scissors that release soluble endoglin from placenta, a toxin centrally responsible for severe preeclampsia. In this project we aim to further investigate the mechanisms governing soluble endoglin release and to begin developing a potential therapeutic for use in the clinic.
Related publications (13)
EGFL7 gene expression is regulated by hypoxia in trophoblast and altered in the plasma of patients with early preeclampsia
Clare L Whitehead, Tu'uhevaha J Kaitu'u-Lino, Natalie K Binder, Sally Beard, Natasha De Alwis, Fiona Brownfoot, Stephen Tong, Natalie J Hannan
INTRODUCTION: Preeclampsia is a severe complication of pregnancy, and likely arises from abnormal placental development in early p..
Key players of the necroptosis pathway RIPK1 and SIRT2 are altered in placenta from preeclampsia and fetal growth restriction
Natalie J Hannan, Sally Beard, Natalie K Binder, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino, Qi Chen, Laura Tuohey, Manarangi De Silva, Stephen Tong
INTRODUCTION: Preeclampsia (PE) and fetal growth restriction (FGR) are among the leading causes of perinatal morbidity and mortali..
Nuclear factor of activated T-cells (NFAT) regulates soluble fms-like tyrosine kinase-1 secretion (sFlt-1) from human placenta
Louie Ye, Amy Gratton, Natalie J Hannan, Ping Cannon, Minh Deo, Kirsten R Palmer, Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Fiona C Brownfoot
INTRODUCTION: Preeclampsia is a serious complication affecting 5-8% of pregnancies. Central to its pathogenesis is placental hypox..
Effects of simvastatin, rosuvastatin and pravastatin on soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) secretion from human umbilical vein endothelial cells, primary trophoblast cells and placenta
Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Roxanne Hastie, Ping Cannon, Tu'uhevaha J Kaitu'u-Lino
BACKGROUND: Preeclampsia is associated with the placental release of soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endog..
Loss of Akt increases soluble endoglin release from endothelial cells but not placenta
Tu'uhevaha J Kaitu'u-Lino, Roxanne Hastie, Natalie J Hannan, Fiona Brownfoot, Manarangi De Silva, Ping Cannon, Laura Tuohey, Stephen Tong
INTRODUCTION: Preeclampsia is a serious pregnancy complication for which there are no medical treatments. Soluble endoglin is an a..
Metformin as a prevention and treatment for preeclampsia: effects on soluble fms-like tyrosine kinase 1 and soluble endoglin secretion and endothelial dysfunction
Fiona C Brownfoot, Roxanne Hastie, Natalie J Hannan, Ping Cannon, Laura Tuohey, Laura J Parry, Sevvandi Senadheera, Sebastian E Illanes, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
BACKGROUND: Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and sol..
Heme Oxygenase-1 Is Not Decreased in Preeclamptic Placenta and Does Not Negatively Regulate Placental Soluble fms-Like Tyrosine Kinase-1 or Soluble Endoglin Secretion
Stephen Tong, Tu'uhevaha J Kaitu'u-Lino, Kenji Onda, Sally Beard, Roxanne Hastie, Natalie K Binder, Cathy Cluver, Laura Tuohey, Clare Whitehead, Fiona Brownfoot, Manarangi De Silva, Natalie J Hannan
Elevated placental release of the antiangiogenic factors, soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sENG),..
YC-1 reduces placental sFlt-1 and soluble endoglin production and decreases endothelial dysfunction: A possible therapeutic for preeclampsia
Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Roxanne Hastie, Ping Cannon, Laura Tuohey, Tu'uhevaha J Kaitu'u-Lino
Preeclampsia is a serious complication of pregnancy with no medical treatment. It is caused by intermittent placental hypoxia and ..
Effects of Pravastatin on Human Placenta, Endothelium, and Women With Severe Preeclampsia
Fiona C Brownfoot, Stephen Tong, Natalie J Hannan, Natalie K Binder, Susan P Walker, Ping Cannon, Roxanne Hastie, Kenji Onda, Tu'uhevaha J Kaitu'u-Lino
UNLABELLED: Preeclampsia is a major pregnancy complication where excess placental release of soluble fms-like tyrosine kinase-1 (s..
Peptides do not prevent cleavage of endoglin to produce soluble endoglin
Roxanne Hastie, Stephen Tong, Ping Cannon, Fiona Brownfoot, Natalie J Hannan, Tu'uhevaha Kaitu'u-Lino
MMP14 cleaves membrane bound endoglin to produce soluble endoglin (sEng), an anti-angiogenic factor that causes endothelial dysfun..
Soluble endoglin production is upregulated by oxysterols but not quenched by pravastatin in primary placental and endothelial cells
FC Brownfoot, N Hannan, K Onda, S Tong, T Kaitu'u-Lino
INTRODUCTION: Preeclampsia is a serious pregnancy complication. Soluble endoglin (sEng) is released from the placenta and contribu..
Galectin-7 acts as an adhesion molecule during implantation and increased expression is associated with miscarriage
EM Menkhorst, T Gamage, C Cuman, TJ Kaitu'u-Lino, S Tong, E Dimitriadis
INTRODUCTION: Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implanta..