Autoimmunity in preeclampsia : the role of angiotensin II type 1 receptor antibodies

  • Shikha Aggarwal

Western Sydney University thesis: Doctoral thesis

Abstract

Preeclampsia pathogenesis is complex and multifactorial. The role of auto-immunity in preeclampsia, specifically angiotensin II type 1 receptor antibodies (AT1AA) has been a point of contentious. This thesis explores the role of AT1AA in human preeclampsia, in an in-vivo experimental model of preeclampsia and in an in-vitro cell culture model of early placental development. A longitudinal retrospective case-control human study was conducted to identify the specificity of AT1AA and their relationship to angiogenic molecules in women with preeclampsia, compared to age matched patients with gestational hypertension or normal blood pressure. The ATIAA did not differ between the three diagnostic groups and there was no relationship to the angiogenic markers assessed (i.e. soluble fms like tyrosine kinase 1 receptor (sFlt-1), placental growth factor (PlGF) and soluble endoglin (sEng). In a non- human primate experimental uteroplacental ischaemia (UPI) model of preeclampsia, ischaemia did not change the AT1AA either acutely or after 14 days. Further work demonstrated, similar to the findings in humans, that there was no significant relationship between AT1AA and both circulating and placental angiogenic markers. Although there was a significant decline in Ang II concentrations after the induction of placental ischemia, there was no relationship with AT1AA. Co-cultures of human uterine microvascular endothelial cells and first trimester trophoblast cells were incubated with AT1AA, Ang II, AT1AA+ Ang II at two oxygen tensions (2% and 21%). The addition of AT1AA to co-cultures incubated at 2% O2 resulted in decreased trophoblast and endothelial cell integration along with decreased mRNA expression of sFlt-1 and sEng. The combination of AT1AA and Ang II in 2% O2 resulted in a further decrease in cellular interactions. Taken together, this thesis demonstrates that AT1AA may affect trophoblast invasion and hence placentation but are not affected by placental ischemia.
Date of Award2020
Original languageEnglish

Keywords

  • preeclampsia
  • pathogenesis
  • autoimmunity
  • angiotensin II

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