Soluble endoglin in the pathogenesis of preeclampsia: investigation of mechanisms and the development of therapeutics

Grant number: 1048707 | Funding period: 2013 - 2015

Completed

Abstract

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

2018-10-01

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

2017-03-01

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

2016-12-01

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

2016-05-20

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

2016-04-01

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

2016-03-01

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

2015-11-01

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

2015-09-15

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

2015-09-01

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

2014-10-01

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

2014-09-01

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

2014-03-01

INTRODUCTION: Galectins are expressed at the fetal-maternal interface and have multiple roles including during blastocyst implanta..

MT-MMPs in pre-eclamptic placenta: Relationship to soluble endoglin production

TJ Kaitu'u-Lino, L Tuohey, L Ye, K Palmer, M Skubisz, S Tong

2013-02-01

INTRODUCTION: Pre-eclampsia is a serious complication of pregnancy, characterized by severe endothelial dysfunction resulting in h..

University of Melbourne Researchers

Tu'uhevaha Lino