title: Lack of modulatory effect of simvastatin on indoxyl sulfate-induced activation of cultured endothelial cells.
abstract: OBJECTIVE
  Endothelial dysfunction is a common manifestation of chronic kidney disease (CKD). The protein-bound uremic toxins have emerged as important factors associated with cardiovascular disease and the outcome of CKD. The effect of indoxyl sulfate (IS) on endothelial cells remains unclear.
  
  
  METHODS
  Human umbilical endothelial cells (HUVEC) were incubated using IS at two concentrations: 100 μM and 1000 μM over two periods of time: 16 and 48 h. HUVEC were also pre-treated with simvastatin to examine its effect. RT-PCR was used to assess changes in the gene expression of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), Monocyte chemotactic protein-1 (MCP-1), E-selectin, and angiotensin receptor type 1 (AT1R). Protein abundance of the investigated molecules was assessed by immunoblotting.
  
  
  RESULTS
  Treatment with 100 μM IS for 16 h induced a 2-fold increase in the expression of ICAM-1, VCAM-1, and MCP-1. At a concentration of 1000 μM, there was a 2-3-fold increase. An extended treatment period at low concentrations was associated with a 2-3 fold increase and the increase of ICAM-1 and VCAM-1 was more prominent under high concentration. Results of immunoblotting confirmed an increase in the abundance of ICAM-1, VCAM-1 and MCP-1. No significant change was noted in E-selectin and AT1R according to concentration or treatment duration. Pre-treatment with simvastatin did not alter IS-induced changes.
  
  
  CONCLUSIONS
  IS increased the expression of adhesion molecules of endothelial cells exhibiting a concentration and duration dependent pattern. Simvastatin did not demonstrate any effect on IS-associated endothelial activation.
authors: Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang-Gung Memorial Hospital and Chang-Gung University College of Medicine, Kaohsiung, Taiwan. chientel@gmail.com
authors: Chien-Te
authors: CT
authors: Lee
authors: Yueh-Ting
authors: YT
authors: Lee
authors: Hwee-Yeong
authors: HY
authors: Ng
authors: Terry Ting-Yu
authors: TT
authors: Chiou
authors: Cheng-I
authors: CI
authors: Cheng
authors: Chien-Chun
authors: CC
authors: Kuo
authors: Chien-Hsing
authors: CH
authors: Wu
authors: Po-Jui
authors: PJ
authors: Chi
authors: Wen-Chin
authors: WC
authors: Lee
mesh_terms: D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007200:Indican / Q000378:metabolism / Q000633:toxicity*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics; D051916:Membrane Cofactor Protein / Q000096:biosynthesis / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019821:Simvastatin; D007200:Indican