The Molecular Pathology of Pre-Eclamptic Hypertension

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...

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Main Authors: Robin W. Carrell, Randy J. Read, Aiwu Zhou
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/5/375
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author Robin W. Carrell
Randy J. Read
Aiwu Zhou
author_facet Robin W. Carrell
Randy J. Read
Aiwu Zhou
author_sort Robin W. Carrell
collection DOAJ
description 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).
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spelling doaj-art-a37d1dd111b547f18710a8a708a449e82025-08-20T01:56:16ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-05-0147537510.3390/cimb47050375The Molecular Pathology of Pre-Eclamptic HypertensionRobin W. Carrell0Randy J. Read1Aiwu Zhou2Department of Haematology, Cambridge Institute for Medical Research, Trinity College, University of Cambridge, Cambridge CB2 1TQ, UKDepartment of Haematology, Cambridge Institute for Medical Research, Trinity College, University of Cambridge, Cambridge CB2 1TQ, UKDepartment of Haematology, Cambridge Institute for Medical Research, Trinity College, University of Cambridge, Cambridge CB2 1TQ, UKThe 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).https://www.mdpi.com/1467-3045/47/5/375angiotensinogenhypertensionpre-eclampsiaS-nitrosylationplacenta redox stress
spellingShingle Robin W. Carrell
Randy J. Read
Aiwu Zhou
The Molecular Pathology of Pre-Eclamptic Hypertension
Current Issues in Molecular Biology
angiotensinogen
hypertension
pre-eclampsia
S-nitrosylation
placenta redox stress
title The Molecular Pathology of Pre-Eclamptic Hypertension
title_full The Molecular Pathology of Pre-Eclamptic Hypertension
title_fullStr The Molecular Pathology of Pre-Eclamptic Hypertension
title_full_unstemmed The Molecular Pathology of Pre-Eclamptic Hypertension
title_short The Molecular Pathology of Pre-Eclamptic Hypertension
title_sort molecular pathology of pre eclamptic hypertension
topic angiotensinogen
hypertension
pre-eclampsia
S-nitrosylation
placenta redox stress
url https://www.mdpi.com/1467-3045/47/5/375
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