非布索坦
别嘌呤醇
尿酸
脐静脉
高尿酸血症
药理学
黄嘌呤氧化酶
医学
化学
内科学
内分泌学
生物化学
酶
体外
作者
Karel H. van der Pol,Jan J. Koenderink,Jeroen J. M. W. van den Heuvel,Petra van den Broek,Janny L. Peters,Imke D. W. van Bunningen,Jeanne Pertijs,Frans G. M. Rüssel,Jim Koldenhof,Wim J. Morshuis,J. van Drongelen,Tom J.J. Schirris,Andries D. van der Meer,Gerard A. Rongen
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2024-06-21
卷期号:19 (6): e0305906-e0305906
标识
DOI:10.1371/journal.pone.0305906
摘要
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.
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