TY - JOUR
T1 - Effects of allopurinol and febuxostat on uric acid transport and transporter expression in human umbilical vein endothelial cells
AU - van der Pol, Karel H.
AU - Koenderink, Jan
AU - van den Heuvel, Jeroen J.M.W.
AU - van den Broek, Petra
AU - Peters, Janny
AU - van Bunningen, Imke D.W.
AU - Pertijs, Jeanne
AU - Russel, Frans G.M.
AU - Koldenhof, Jim
AU - Morshuis, Wim J.
AU - van Drongelen, Joris
AU - Schirris, Tom J.J.
AU - van der Meer, Andries
AU - Rongen, Gerard A.
N1 - Publisher Copyright:
© 2024 van der Pol et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2024/6/21
Y1 - 2024/6/21
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85196807726&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0305906
DO - 10.1371/journal.pone.0305906
M3 - Article
C2 - 38905201
AN - SCOPUS:85196807726
SN - 1932-6203
VL - 19
JO - PLoS ONE
JF - PLoS ONE
IS - 6
M1 - e0305906
ER -