N-Acetylcysteine and Sulodexide Reduce the Prothrombotic Effect of Uremic Serum on the Venous Endothelial Cells.
Acetylcysteine
/ pharmacology
Anticoagulants
Blood Specimen Collection
Cells, Cultured
Endothelial Cells
/ drug effects
Endothelium, Vascular
/ cytology
Female
Free Radical Scavengers
Glycosaminoglycans
/ pharmacology
Humans
Kidney Failure, Chronic
/ blood
Male
Thrombosis
/ prevention & control
Uremia
/ blood
N-acetylcysteine
Sulodexide
Uremia
Venous endothelium
Journal
Kidney & blood pressure research
ISSN: 1423-0143
Titre abrégé: Kidney Blood Press Res
Pays: Switzerland
ID NLM: 9610505
Informations de publication
Date de publication:
2019
2019
Historique:
received:
25
02
2019
accepted:
17
03
2019
pubmed:
9
4
2019
medline:
18
12
2019
entrez:
9
4
2019
Statut:
ppublish
Résumé
Thromboembolic episodes are a frequent problem in end stage renal failure patients. The pathomechanism of the disorder is complex, including bioincompatibility of renal replacement therapy, endothelial dysfunction, increased blood level of procoagulant factors and uremic toxins. We studied changes in the functional properties of venous endothelial cells (VEC) in the presence of uremic serum and evaluated their possible modulation by N-acetylcysteine (NAC) or sulodexide (SUL). Serum samples from 12 uremic patients treated with hemodialysis were studied ex vivo on in vitro cultured VEC. In separate experiments, NAC 1 mmol/L or SUL 0.5 LRU/mL were added to uremic serum samples. Both changes in the gene expression and secretory activity of VEC were studied. Uremic serum increased the expression of the following genes: IL6 +97%, p < 0.002; VEGF +28%, p < 0.002; vWF +47%, p < 0.002; PECAM +76%, p < 0.002; ICAM-1 +275%, p < 0.002; t-PA +96%, p < 0.002. Changes in gene expression were reflected by the increased secretory activity of VEC treated with the uremic serum. Exposure of VEC to uremic serum supplemented with NAC or SUL resulted in weaker stimulation of the studied genes' expression. Also, secretion of the studied solutes, with the exception of ICAM-1, was reduced in the presence of NAC: IL6 -34%, p < 0.01; VEGF -40%, p < 0.005; vWF -25%, p < 0.001; t-PA -47%, p < 0.01, and MMP9 -37%, p < 0.001. SUL reduced the uremic serum-induced secretion of all solutes: IL6 -24%, p < 0.05; ICAM-1 -43%, p < 0.01; VEGF -38%, p < 0.01; vWF -23%, p < 0.01; t-PA -49%, p < 0.01, and MMP9 -25%, p < 0.05. Uremic serum induces prothrombotic changes in VEC, which may cause a predisposition to thrombotic disorders in patients with renal failure. NAC and SUL reduce the effects of the uremic serum in VEC, which suggests their potential therapeutic application in uremic patients.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
Thromboembolic episodes are a frequent problem in end stage renal failure patients. The pathomechanism of the disorder is complex, including bioincompatibility of renal replacement therapy, endothelial dysfunction, increased blood level of procoagulant factors and uremic toxins. We studied changes in the functional properties of venous endothelial cells (VEC) in the presence of uremic serum and evaluated their possible modulation by N-acetylcysteine (NAC) or sulodexide (SUL).
METHODS
METHODS
Serum samples from 12 uremic patients treated with hemodialysis were studied ex vivo on in vitro cultured VEC. In separate experiments, NAC 1 mmol/L or SUL 0.5 LRU/mL were added to uremic serum samples. Both changes in the gene expression and secretory activity of VEC were studied.
RESULTS
RESULTS
Uremic serum increased the expression of the following genes: IL6 +97%, p < 0.002; VEGF +28%, p < 0.002; vWF +47%, p < 0.002; PECAM +76%, p < 0.002; ICAM-1 +275%, p < 0.002; t-PA +96%, p < 0.002. Changes in gene expression were reflected by the increased secretory activity of VEC treated with the uremic serum. Exposure of VEC to uremic serum supplemented with NAC or SUL resulted in weaker stimulation of the studied genes' expression. Also, secretion of the studied solutes, with the exception of ICAM-1, was reduced in the presence of NAC: IL6 -34%, p < 0.01; VEGF -40%, p < 0.005; vWF -25%, p < 0.001; t-PA -47%, p < 0.01, and MMP9 -37%, p < 0.001. SUL reduced the uremic serum-induced secretion of all solutes: IL6 -24%, p < 0.05; ICAM-1 -43%, p < 0.01; VEGF -38%, p < 0.01; vWF -23%, p < 0.01; t-PA -49%, p < 0.01, and MMP9 -25%, p < 0.05.
CONCLUSIONS
CONCLUSIONS
Uremic serum induces prothrombotic changes in VEC, which may cause a predisposition to thrombotic disorders in patients with renal failure. NAC and SUL reduce the effects of the uremic serum in VEC, which suggests their potential therapeutic application in uremic patients.
Identifiants
pubmed: 30959503
pii: 000499879
doi: 10.1159/000499879
doi:
Substances chimiques
Anticoagulants
0
Free Radical Scavengers
0
Glycosaminoglycans
0
glucuronyl glucosamine glycan sulfate
75HGV0062C
Acetylcysteine
WYQ7N0BPYC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
277-285Informations de copyright
© 2019 The Author(s) Published by S. Karger AG, Basel.