Effects of allopurinol and febuxostat on uric acid transport and transporter expression in human umbilical vein endothelial cells

Uric acid induces radical oxygen species formation, endothelial inflammation, and endothelial dysfunction which contributes to the progression of atherosclerosis. Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that...

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Veröffentlicht in:PloS one 2024-06, Vol.19 (6), p.e0305906
Hauptverfasser: van der Pol, Karel H, Koenderink, Jan, van den Heuvel, Jeroen J M W, van den Broek, Petra, Peters, Janny, van Bunningen, Imke D W, Pertijs, Jeanne, Russel, Frans G M, Koldenhof, Jim, Morshuis, Wim J, van Drongelen, Joris, Schirris, Tom J J, van der Meer, Andries, Rongen, Gerard A
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container_issue 6
container_start_page e0305906
container_title PloS one
container_volume 19
creator van der Pol, Karel H
Koenderink, Jan
van den Heuvel, Jeroen J M W
van den Broek, Petra
Peters, Janny
van Bunningen, Imke D W
Pertijs, Jeanne
Russel, Frans G M
Koldenhof, Jim
Morshuis, Wim J
van Drongelen, Joris
Schirris, Tom J J
van der Meer, Andries
Rongen, Gerard A
description Uric acid induces radical oxygen species formation, endothelial inflammation, and endothelial dysfunction which contributes to the progression of atherosclerosis. Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake by human umbilical vein endothelial cells. Febuxostat increased intracellular uric acid concentrations compared with control. In contrast, allopurinol did not affect intracellular uric acid concentration. In line with this observation, febuxostat increased mRNA expression of GLUT9 and reduced MRP4 expression, while allopurinol did not affect mRNA expression of these uric acid transporters. These findings provide a possible pathophysiological pathway which could explain the higher cardiovascular mortality for febuxostat compared to allopurinol but should be explored further.
doi_str_mv 10.1371/journal.pone.0305906
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Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake by human umbilical vein endothelial cells. Febuxostat increased intracellular uric acid concentrations compared with control. In contrast, allopurinol did not affect intracellular uric acid concentration. In line with this observation, febuxostat increased mRNA expression of GLUT9 and reduced MRP4 expression, while allopurinol did not affect mRNA expression of these uric acid transporters. 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Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake by human umbilical vein endothelial cells. Febuxostat increased intracellular uric acid concentrations compared with control. In contrast, allopurinol did not affect intracellular uric acid concentration. In line with this observation, febuxostat increased mRNA expression of GLUT9 and reduced MRP4 expression, while allopurinol did not affect mRNA expression of these uric acid transporters. 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Febuxostat inhibits BCRP- and allopurinol stimulates MRP4-mediated uric acid efflux in human embryonic kidney cells. We hypothesized that endothelial cells express uric acid transporters that regulate intracellular uric acid concentration and that modulation of these transporters by febuxostat and allopurinol contributes to their different impact on cardiovascular mortality. The aim of this study was to explore a potential difference between the effect of febuxostat and allopurinol on uric acid uptake by human umbilical vein endothelial cells. Febuxostat increased intracellular uric acid concentrations compared with control. In contrast, allopurinol did not affect intracellular uric acid concentration. In line with this observation, febuxostat increased mRNA expression of GLUT9 and reduced MRP4 expression, while allopurinol did not affect mRNA expression of these uric acid transporters. These findings provide a possible pathophysiological pathway which could explain the higher cardiovascular mortality for febuxostat compared to allopurinol but should be explored further.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>38905201</pmid><doi>10.1371/journal.pone.0305906</doi><tpages>e0305906</tpages><orcidid>https://orcid.org/0000-0002-3064-3192</orcidid><orcidid>https://orcid.org/0000-0002-7959-2314</orcidid><orcidid>https://orcid.org/0000-0001-5345-9788</orcidid><oa>free_for_read</oa></addata></record>
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subjects Allopurinol
Allopurinol - pharmacology
Analysis
Arteriosclerosis
Atherosclerosis
Biological Transport - drug effects
Biology and Life Sciences
Cardiovascular diseases
Clinical trials
Development and progression
Disease
Efflux
Endothelial cells
Endothelium
Epidermal growth factor
Febuxostat - pharmacology
Gene expression
Gene Expression Regulation - drug effects
Glucose
Glucose Transport Proteins, Facilitative - genetics
Glucose Transport Proteins, Facilitative - metabolism
Health aspects
Hospitals
Human Umbilical Vein Endothelial Cells - drug effects
Human Umbilical Vein Endothelial Cells - metabolism
Humans
Inflammation
Intracellular
Kidneys
Medicine and Health Sciences
Mortality
Multidrug Resistance-Associated Proteins - genetics
Multidrug Resistance-Associated Proteins - metabolism
Penicillin
Physical Sciences
Proteins
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
Thoracic surgery
Umbilical cord
Umbilical vein
Uric acid
Uric Acid - metabolism
Veins & arteries
title Effects of allopurinol and febuxostat on uric acid transport and transporter expression in human umbilical vein endothelial cells
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