Pravastatin Corrects Endothelial Dysfunction in Ex Vivo Uterine Radial Arteries in Preeclampsia

Nathan M. Luque; Leo Leader; Sandra M. Lowe; Steven D. Horrowitz; Marianne Tare; Victoria Hinkley; Vladimir V. Matchkov; Maged M. Costantine; Irit Markus; Lu Liu; Shaun L. Sandow; Timothy V. Murphy

doi:10.1111/apha.70186

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Pravastatin Corrects Endothelial Dysfunction in Ex Vivo Uterine Radial Arteries in Preeclampsia

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Pravastatin Corrects Endothelial Dysfunction in Ex Vivo Uterine Radial Arteries in Preeclampsia

Nathan M. Luque, Leo Leader, Sandra M. Lowe, Steven D. Horrowitz, Marianne Tare, Victoria Hinkley, Vladimir V. Matchkov, Maged M. Costantine, Irit Markus, Lu Liu, …

Acta Physiologica, Vol.242(4), pp.1-16

2026

DOI: https://doi.org/10.1111/apha.70186

PMCID: PMC12976587

PMID: 41808442

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Abstract

calcium-activated potassium channels

caveolae

endothelium-dependent dilation

gap junction

nitric oxide

Aim Endothelium-dependent relaxation in isolated uterine radial arteries from normotensive (NT) and preeclamptic (PE) pregnancies, and the acute effects of pravastatin in the latter vessels were assessed. Pravastatin is hypothesized to alleviate endothelial dysfunction in PE via modulating aspects of NO and endothelium-derived hyperpolarization-mediated relaxation. Methods Radial arteries isolated from the uterus of NT and PE pregnant patients were incubated with pravastatin (2 mM/6 h), methyl-β-cyclodextrin (10 mM/1 h) in vitro, or vehicle. Vessel function was determined with pressure myography, while related morphology and protein/mRNA expression were characterized using immunohistochemistry, electron microscopy, and qPCR. Results Endothelium-dependent, bradykinin-induced NO-mediated relaxation was impaired in radial arteries from PE compared to NT pregnancy, with a reduced intermediate- and large-conductance Ca2+-activated K+-channel contribution. Endothelial small-conductance Ca2+-activated K+-channel function and expression were increased in arteries from PE, compared to NT patients. Pravastatin restored NO and endothelium-derived hyperpolarization-mediated relaxation in arteries from PE women; potentially overcompensating overall endothelium-dependent relaxation. Myoendothelial gap junction and endothelial caveolae density, and caveolin-1 and endothelial-NOS expression were decreased in arteries from PE relative to NT pregnancies and increased following pravastatin incubation. Caveolae density in NT patient arteries was reduced by methyl-β-cyclodextrin, while endothelial caveolae were increased in vessels from PE patients. Pravastatin incubation restored endothelial function via improved NO and endothelium-derived hyperpolarization-type mechanisms. Conclusions Pravastatin restored endothelium-dependent relaxation in uterine radial arteries from PE pregnancies. Data support the therapeutic potential for pravastatin in treating PE, with ongoing trials determining the validity of its use in the clinical setting. Trial Registration ClinicalTrials.gov identifier: NCT01717586

Details

Title: Pravastatin Corrects Endothelial Dysfunction in Ex Vivo Uterine Radial Arteries in Preeclampsia
Authors: Nathan M. Luque (Corresponding Author) - UNSW Sydney
Leo Leader - Royal Hospital for Women
Sandra M. Lowe - Royal Hospital for Women
Steven D. Horrowitz - Royal Hospital for Women
Marianne Tare - Monash Health
Victoria Hinkley - University of the Sunshine Coast
Vladimir V. Matchkov - Aarhus University
Maged M. Costantine - The Ohio State University Wexner Medical Center
Irit Markus - UNSW Sydney
Lu Liu - UNSW Sydney
Shaun L. Sandow - University of the Sunshine Coast
Timothy V. Murphy - UNSW Sydney
Publication details: Acta Physiologica, Vol.242(4), pp.1-16
Publisher: Wiley-Blackwell Publishing Ltd.
Date published: 2026
DOI: 10.1111/apha.70186
ISSN: 1748-1716
PMID: 41808442; PMC12976587
Copyright note: © 2026 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Data Availability: Data are available from the corresponding author upon reasonable request.
Grants: Identifying key components of cerebrovascular signalling in health and disease, 0980028303, University of the Sunshine Coast (Australia, Sunshine Coast) - UniSC
Organisation Unit: School of Health - Biomedicine; Healthy Ageing Research Cluster
Language: English
Record Identifier: 991219352602621
Output Type: Journal article

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