Abstract | BACKGROUND:
Cardiovascular diseases are the major causes of mortality in uremic patients, and the vascular endothelium is dysfunctional in uremia. We hypothesized that uremic retention solutes may be among the factors involved in this endothelial dysfunction. We therefore investigated the in vitro effect of a large panel of uremic retention solutes (guanidino compounds, polyamines, oxalate, myoinositol, urea, uric acid, creatinine, indoxyl sulfate, indole-3- acetic acid, p-cresol, hippuric acid, and homocysteine) on endothelial proliferation. In addition, we tested the effect of uremic solutes that altered proliferation on endothelial wound repair. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with uremic retention solutes at concentrations in the range found in uremic patients. Protein-bound uremic solutes were also tested in the presence of 4% human albumin. Then, we determined the effect of each uremic solute on endothelial proliferation by a 5-bromo-2-deoxy-uridine ( BrdU) labeling assay. In addition, confluent endothelial monolayers were injured, incubated with uremic solutes that altered endothelial proliferation, and the surface of the wound was measured at different intervals by image analysis. RESULTS: CONCLUSION: We demonstrated that both p-cresol and indoxyl sulfate decrease endothelial proliferation and wound repair. These solutes could play a role in endothelial dysfunction observed in uremic patients.
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Authors | Laetitia Dou, Emilie Bertrand, Claire Cerini, Valerie Faure, Jose Sampol, Raymond Vanholder, Yvon Berland, Philippe Brunet |
Journal | Kidney international
(Kidney Int)
Vol. 65
Issue 2
Pg. 442-51
(Feb 2004)
ISSN: 0085-2538 [Print] United States |
PMID | 14717914
(Publication Type: Journal Article)
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Chemical References |
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Topics |
- Apoptosis
(drug effects)
- Cell Division
(drug effects)
- Cell Survival
(drug effects)
- Cells, Cultured
- Cresols
(pharmacology)
- Endothelium, Vascular
(cytology, drug effects)
- Humans
- Indican
(pharmacology)
- Umbilical Veins
(cytology)
- Uremia
(metabolism, pathology)
- Wound Healing
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