title: Uremic serum induces proatherogenic changes in human endothelial cells.
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 mononuclear 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. (alfa2)IV collagen, tissue inhibitor of metalloproteases-1 (TIMP-1) and transforming growth factor-beta (TGF-beta) mRNA levels were measured by reverse transcriptase polymerase chain reaction (RT-PCR). In some experiments cells were preincubated with anti-receptor 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 (alfa2)IV collagen, TIMP-1 and TGF-beta mRNA levels. There was no increase in nitric oxide concentration in ure-mic serum-treated endothelial cells, and the expression of TGF-beta 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.
authors.affiliation: Unit of Nephrology, Dialysis and Transplantation, IRCCS Policlinico San Matteo, University of Pavia, Pavia-Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Fasoli
authors.forename: Ciro
authors.initials: C
authors.lastname: Esposito
authors.forename: Flavia
authors.initials: F
authors.lastname: Cornacchia
authors.forename: Andreana
authors.initials: A
authors.lastname: De Mauri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Grosjean
authors.forename: Filippo
authors.initials: F
authors.lastname: Mangione
authors.forename: AnnaRita
authors.initials: A
authors.lastname: Plati
authors.forename: Luigi
authors.initials: L
authors.lastname: Villa
authors.forename: Antonio
authors.initials: A
authors.lastname: Dal Canton
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D024141:Collagen Type IV; D003324:Coronary Artery Disease / Q000209:etiology* / Q000378:metabolism* / Q000401:mortality; D042783:Endothelial Cells; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D044967:Serum / Q000378:metabolism*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014511:Uremia / Q000150:complications* / Q000378:metabolism* / Q000401:mortality
chemical_list: D000911:Antibodies, Monoclonal; D024141:Collagen Type IV; D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester