Uremic serum induces proatherogenic changes in human endothelial cells

Gianluca Fasoli, Ciro Esposito, Flavia Cornacchia, Andreana De Mauri, Fabrizio Grosjean, Filippo Mangione, AnnaRita R. Plati, Luigi Villa, Antonio Dal Canton

Research output: Contribution to journalArticle

Abstract

Background: Cardiovascular complications are the main cause of death in uremic patients. Uremic angiopathy has been regarded as an accelerated form of atherosclerosis. However the mechanism leading to vessel wall injury is still unknown. We hypothesized that uremic serum affects endothelium inducing a proatherogenic state. Methods: We studied the effects of uremic serum on human endothelial cells (HECs). Cell proliferation and adhesion of mononudear cells to HEC monolayers were evaluated by cell counting, apoptosis and collagen production by ELISA, and nitric oxide (NO) by measuring the concentration of nitrite/nitrate in the cell supernatant. (αx2)IV collagen, tissue inhibitor of metalloproteases-1 (TIMP-1) and transforming growth factor-β (TGF-β) mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR). In some experiments cells were preincubated with antireceptor for advanced glycation end product (anti-RAGE) blocking antibodies. Results: Uremic serum did not modify HEC proliferation but induced apoptosis after 72 hours of incubation. Adhesion of mononuclear cells to HEC monolayers was significantly increased by uremic serum. In addition, uremic serum increased (α2)IV collagen, TIMP-1 and TGF-β mRNA levels. There was no increase in nitric oxide concentration in uremic serum-treated endothelial cells, and the expression of TGF-β was neither modified by L-NAME nor by anti-RAGE antibodies. Conclusions: Our results indicate that uremic serum affects HEC inducing a proatherogenic state that may be responsible for the accelerated atherosclerosis of uremic patients. Apparently uremic serum effect is not mediated by NO or by AGEs.

Original languageEnglish
Pages (from-to)599-604
Number of pages6
JournalJournal of Nephrology
Volume19
Issue number5
Publication statusPublished - Sep 2006

Keywords

  • Atherosclerosis
  • Endothelial cells
  • TGF-β
  • Uremia

ASJC Scopus subject areas

  • Nephrology

Fingerprint Dive into the research topics of 'Uremic serum induces proatherogenic changes in human endothelial cells'. Together they form a unique fingerprint.

  • Cite this

    Fasoli, G., Esposito, C., Cornacchia, F., De Mauri, A., Grosjean, F., Mangione, F., Plati, A. R., Villa, L., & Dal Canton, A. (2006). Uremic serum induces proatherogenic changes in human endothelial cells. Journal of Nephrology, 19(5), 599-604.