NDLI: Effect of uraemia on endothelial cell damage is mediated by the integrin linked kinase pathway

Content Provider	PubMed Central
Author	Andrea, García-jérez Luengo, Alicia Carracedo, Julia Rafael, Ramírez-chamond Diego, Rodriguez-puyol Manuel, Rodriguez-puyol Calleros, Laura
Copyright Year	2014
Abstract	Patients with chronic kidney disease (CKD) have a higher risk of developing cardiovascular diseases. Their vascular endothelium is dysfunctional, among other things, because it is permanently exposed to uraemic toxins, several of which, mostly protein-bound compounds such as indoxyl sulfate (IS) and p-cresyl sulphate, having poor clearance by conventional dialysis, induce endothelial toxicity. However, the molecular mechanism by which uraemic toxins regulate early stages of endothelial dysfunction remains unclear. Recent studies have demonstrated the important role of integrin-linked kinase (ILK) in the maintenance of endothelial integrity. In this study, we investigate the involvement of ILK in the mechanism underlying vascular endothelial damage that occurs in uraemia. First, we show that incubation of EA.hy926 cells with human uraemic serum from CKD patients upregulates ILK activity. This ILK activation also occurs when the cells are exposed to IS (25–100 μg ml−1), p-cresol (10–100 μg ml−1) or both combined, compared to human serum control. Next, we observed that high doses of both toxins together induce a slight decrease in cell proliferation and increase apoptosis and reactive oxygen species production. Interestingly, these toxic effects displayed a strong increase when the ILK protein is knocked down by small interfering RNA, even at low doses of uraemic toxins. Abrogation of AKT has demonstrated the ILK/AKT signalling pathway involved in these processes. This study has demonstrated the implication of ILK in the protection against endothelial cell damage induced by uraemic toxins, a molecular mechanism that could play a protective role in the early stages of endothelial dysfunction observed in uraemic patients.
Related Links	http://dx.doi.org/10.1113/jphysiol.2014.283887
Ending Page	618
Page Count	18
Starting Page	601
File Format	PDF
ISSN	14697793
e-ISSN	14697793
Journal	The Journal of Physiology
Issue Number	Pt 3
Volume Number	593
Language	English
Publisher	BlackWell Publishing Ltd
Publisher Date	2015-02-01
Access Restriction	Open
Rights Holder	BlackWell Publishing Ltd
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Physiology Sports Science

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