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

摘要: Key points Patients with chronic kidney disease have a higher risk of developing cardiovascular diseases than the general population. Their vascular endothelium is dysfunctional, among other things, because it permanently exposed to uraemic toxins, several which poor clearance by conventional dialysis. Recent studies demonstrated important role integrin-linked kinase (ILK) in maintenance endothelial integrity and this study we investigate involvement ILK mechanism underlying damage that occurs uraemia. For first time, demonstrate implication protection against cell (inhibition proliferation, toxicity, oxidative stress programed death) induced serum from patients toxins. This molecular may clinical relevance highlights importance maintaining high levels activity help preserve integrity, at least early stages disease. Abstract Patients (CKD) diseases. which, mostly protein-bound compounds such as indoxyl sulfate (IS) p-cresyl sulphate, having dialysis, induce toxicity. However, toxins regulate dysfunction remains unclear. Recent integrity. In study, uraemia. First, show incubation EA.hy926 cells human CKD upregulates activity. This activation also when are IS (25–100 μg ml−1), p-cresol (10–100 μg ml−1) or both combined, compared control. Next, observed doses together slight decrease proliferation increase apoptosis reactive oxygen species production. Interestingly, these toxic effects displayed strong protein knocked down small interfering RNA, even low toxins. Abrogation AKT has ILK/AKT signalling pathway involved processes. could play protective patients.