4.5 Article

Uremic serum induces prothrombotic changes in venous endothelial cells and inflammatory changes in aortic endothelial cells

Journal

RENAL FAILURE
Volume 43, Issue 1, Pages 401-405

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/0886022X.2021.1890617

Keywords

Aortic endothelium; venous endothelium; uremia; thrombosis; inflammation

Funding

  1. National Science Center, Poland [OPUS 2017/27/B/NZ4/01675]
  2. IUVENTUS Plus [0733/IP1/2016/74]

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Uremia induces different effects on venous endothelial cells (VEC) and aortic endothelial cells (AEC) in terms of gene expression and secretory activity. VEC show increased expression of genes related to coagulation, while AEC exhibit increased expression of genes related to inflammation.
Background Uremia induces various pathologic changes in the endothelium. However, there is limited information about the differences of these effects in endothelial cells originating from different parts of the vascular tree. Methods The effect of uremic serum obtained from patients with end stage renal failure on the gene expression and secretory activity of venous endothelial cells (VEC) and aortic endothelial cells (AEC) was studied in in vitro culture. Results In VEC, the expression of genes regulating the synthesis of von Willebrand factor (vWF) was increased by 254% (p<.005), vascular endothelial growth factor (VEGF) synthesis by 150% (p<.001), tissue plasminogen activator (t-PA) synthesis by 62% (p<.005), platelet endothelial cell adhesion molecule by 89% (p<.005), and the expression of gene regulating interleukin-6 (IL-6) synthesis was reduced. In AEC, the expression of the gene regulating synthesis of IL-6 was increased by 174% (p<.001), and the expression of the other genes was reduced. The secretion of IL-6 was reduced in VEC by 38% (p<.01) and increased in AEC by 55% (p<.005). In VEC, increased synthesis of VEGF 64% (p<.001) vWF (+34%, p<.01), and t-PA (+53%, p<.002) was observed, and in AEC it was reduced. Conclusions VEC and AEC respond in different ways after exposure to uremic serum. VEC acquires the prothrombotic phenotype, whereas in AEC the inflammatory phenotype appears.

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