Activin signalling and pre-eclampsia: from genetic risk to pre-symptomatic biomarker

Cytokine. 2015 Feb;71(2):360-5. doi: 10.1016/j.cyto.2014.11.017. Epub 2014 Dec 13.

Abstract

Pre-eclampsia is a multi-system condition in pregnancy that is characterised by the onset of hypertension and proteinuria in women after the 20th week and it remains a leading cause of maternal and fetal mortality. Despite this the causative molecular basis of pre-eclampsia remains poorly understood. As a result, an intensive research effort has focused on understanding the molecular mechanisms involved in pre-eclampsia and using this information to identify new pre-symptomatic bio-markers of the condition. Activin A and its receptor, ACVR2A, have been extensively studied in this regard. Activin A is a member of the transforming growth factor (TGF)-β superfamily that has a wide range of biological functions depending on the cellular context. Recent work has shown that polymorphisms in ACVR2A may be a genetic risk factor for pre-eclampsia. Furthermore, both placenta and serum levels of Activin A are significantly increased in pre-eclampsia suggesting that Activin A may be a possible biomarker for the condition. Here we review the latest advances in this field and link these with new molecular data that suggest that the oxidative stress and pro-inflammatory cytokine production seen in pre-eclampsia may result in increased placental Activin A secretion in an attempt to maintain placental function.

Keywords: ACVR2A; Activin A; Biomarker; Pre-eclampsia; Serum.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Activins / physiology*
  • Biomarkers / metabolism*
  • Clinical Trials as Topic
  • Cytokines / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation
  • Oxidative Stress
  • Placenta / metabolism
  • Polymorphism, Genetic
  • Pre-Eclampsia / diagnosis*
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Risk Factors
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism

Substances

  • Biomarkers
  • Cytokines
  • Transforming Growth Factor beta
  • Activins