# The Molecular Pathology of Pre-Eclamptic Hypertension

## TL;DR

This paper explores how angiotensinogen and redox-sensitive changes in the placenta contribute to high blood pressure in pre-eclampsia during pregnancy.

## Contribution

The study reveals a novel molecular mechanism involving a redox-sensitive disulphide bridge in angiotensinogen linked to pre-eclamptic hypertension.

## Key findings

- Angiotensinogen structures clarify molecular events leading to pre-eclamptic hypertension.
- A redox-sensitive disulphide bridge modulates release of a vasopressor peptide from angiotensinogen.
- Placental oxidative stress activates a thiol-switch in angiotensinogen, contributing to hypertension.

## Abstract

The central role of angiotensinogen in the control of blood pressure is revealed by a series of crystallographic structures, including complexes with renin. Specifically, the structures provide an understanding of the sequential molecular events that lead to the pre-eclamptic hypertensive crises of pregnancy. The release of the precursor vasopressor peptide from the amino-terminal tail of angiotensinogen appears to be modulated by a redox-sensitive disulphide bridge. Our findings indicate that the activation of the thiol-switch in the circulating maternal angiotensinogen occurs at the placental level in response to oxidative stress, exacerbated by placental insufficiency. We propose here that a contributory factor is the inherent redox stress accompanying the placental exchange of oxygenation between the haemoglobin of the mother (oxy-HbA) and the deoxygenated haemoglobin of the foetus (deoxy-HbF).