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Erschienen in: Angiogenesis 3/2013

01.07.2013 | Original Paper

In acute kidney injury, indoxyl sulfate impairs human endothelial progenitor cells: modulation by statin

verfasst von: Vin-Cent Wu, Guang-Huar Young, Po-Hsun Huang, Shyh-Chyi Lo, Kuo-Chuan Wang, Chiao-Yin Sun, Chan-Jung Liang, Tao-Ming Huang, Jou-Han Chen, Fan-Chi Chang, Yuh-Lien Chen, Yih-Shing Kuo, Jin-Bor Chen, Jaw-Wen Chen, Yung-Ming Chen, Wen-Jo Ko, Kwan-Dun Wu, The NSARF group

Erschienen in: Angiogenesis | Ausgabe 3/2013

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Abstract

Renal ischemia rapidly mobilizes endothelial progenitor cells (EPCs), which provides renoprotection in acute kidney injury (AKI). Indoxyl sulfate (IS) is a protein-binding uremic toxin with a potential role in endothelial injury. In this study, we examined the effects and mechanisms of action of IS on EPCs in AKI. Forty-one consecutive patients (26 male; age, 70.1 ± 14.1 years) diagnosed with AKI according to the AKIN criteria were enrolled. The AKI patients had higher serum IS levels than patients with normal kidney function (1.35 ± 0.94 × 10−4M vs. 0.02 ± 0.02 × 10−4M, P < 0.01). IS levels were negatively correlated to the number of double-labeled (CD34+KDR+) circulating EPCs (P < 0.001). After IS stimulation, the cells displayed decreased expression of phosphorylated endothelial nitric oxide (NO) synthase, vascular cell adhesion molecule-1, increased reactive oxygen species, decreased proliferative capacity, increased senescence and autophagy, as well as decreased migration and angiogenesis. These effects of IS on EPCs were reversed by atorvastatin. Further, exogenous administration of IS significantly reduced EPC number in Tie2-GFP transgenic mice and attenuated NO signaling in aortic and kidney arteriolar endothelium after kidney ischemia–reperfusion injury in mice, and these effects were restored by atorvastatin. Our results are the first to demonstrate that circulating IS is elevated in AKI and has direct effects on EPCs via NO-dependent mechanisms both in vitro and in vivo. Targeting the IS-mediated pathways by NO-releasing statins such as atorvastatin may preempt disordered vascular wall pathology, and represent a novel EPC-rescued approach to impaired neovascularization after AKI.
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Metadaten
Titel
In acute kidney injury, indoxyl sulfate impairs human endothelial progenitor cells: modulation by statin
verfasst von
Vin-Cent Wu
Guang-Huar Young
Po-Hsun Huang
Shyh-Chyi Lo
Kuo-Chuan Wang
Chiao-Yin Sun
Chan-Jung Liang
Tao-Ming Huang
Jou-Han Chen
Fan-Chi Chang
Yuh-Lien Chen
Yih-Shing Kuo
Jin-Bor Chen
Jaw-Wen Chen
Yung-Ming Chen
Wen-Jo Ko
Kwan-Dun Wu
The NSARF group
Publikationsdatum
01.07.2013
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 3/2013
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-013-9339-8

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