The differential placental expression of ERp44 and pre-eclampsia; association with placental zinc, the ERAP1 and the renin-angiotensin-system.


Journal

Placenta
ISSN: 1532-3102
Titre abrégé: Placenta
Pays: Netherlands
ID NLM: 8006349

Informations de publication

Date de publication:
24 03 2023
Historique:
received: 09 12 2022
revised: 06 02 2023
accepted: 21 02 2023
pubmed: 28 2 2023
medline: 15 3 2023
entrez: 27 2 2023
Statut: ppublish

Résumé

Endoplasmic reticulum resident protein 44 (ERp44) is a zinc-metalloprotein, regulating Endoplasmic reticulum aminopeptidase 1 (ERAP1) and Angiotensin II (Ang II). We explored placental ERp44 expression and components of the renin-angiotensin-system (RAS) in pre-eclampsia (PE), correlating these to ERAP1 expression and placental zinc concentrations. Placental tissue, taken at time of delivery in normotensive women or women with PE (n = 12/group), were analysed for ERp44, AT1R, AT2R and AT4R by qPCR. Protein ERp44 expression was measured by immunohistochemistry and compared to previously measured ERAP1 expression. Placental zinc was measured by inductively-coupled-mass-spectrometry. ERp44 gene/protein expression were increased in PE (P < 0.05). AT1R expression was increased (P = 0.02) but AT4R decreased (P = 0.01) in PE, compared to normotensive controls. A positive association between ERp44 and AT2R expression was observed in all groups. ERp44 was negatively correlated with ERAP1 protein expression in all samples. Placental zinc concentrations were lower in women with PE (P = 0.001) and negatively associated with ERp44 gene expression. Increased placental ERp44 could further reduce ERAP1 release in PE, potentially preventing release of Ang IV and thus lowering levels of Ang IV which consequently diminishes the possibility of counterbalancing the activity of vasoconstrictive, Ang II. The lower placental zinc may contribute to dysfunction of the ERp44/ERAP1 complex, exacerbating the hypertension in PE.

Identifiants

pubmed: 36848863
pii: S0143-4004(23)00038-3
doi: 10.1016/j.placenta.2023.02.006
pmc: PMC10682376
pii:
doi:

Substances chimiques

Renin EC 3.4.23.15
Zinc J41CSQ7QDS
Angiotensin II 11128-99-7
ERP44 protein, human 0
Membrane Proteins 0
Molecular Chaperones 0
ERAP1 protein, human EC 3.4.11.-
Aminopeptidases EC 3.4.11.-
Minor Histocompatibility Antigens 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

9-14

Subventions

Organisme : British Heart Foundation
ID : FS/15/32/31604
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P027938/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 217123/Z/19/Z
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom

Informations de copyright

Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest None.

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Auteurs

Rhea Raghu (R)

Tenafly High School, Tenafly, USA. Electronic address: 23rraghu@tenafly.k12.nj.us.

Lesia O Kurlak (LO)

Stroke Trials Unit (School of Medicine), University of Nottingham, Nottingham, UK. Electronic address: lesia.kurlak@nottingham.ac.uk.

Eun D Lee (ED)

Virginia Commonwealth University School of Medicine, Richmond, USA. Electronic address: eun.lee@vcuhealth.org.

Hiten D Mistry (HD)

Division of Women and Children's Health, School of Life Course and Population Sciences, King's College London, London, UK. Electronic address: hiten.mistry@kcl.ac.uk.

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Classifications MeSH