title: Apoptosis in endothelial cells by cyclosporine.
abstract: OBJECTIVE
  The immunosuppressive drug cyclosporine (CsA) is a potent agent widely used after organ transplantations and to treat various autoimmune disorders. After using CsA, some patients suffer severe complications including renal and vascular toxicity, which are influenced by the degree of the endothelial damage. Several studies have demonstrated CsA treatment to directly induce apoptosis in several cell types. Thus, CsA may induce endothelial damage via activation of proapoptotic proteins. The present study was undertaken to investigate the effects of CsA on apoptosis of endothelial cells using human umbilical vein endothelial cells.
  
  
  METHODS
  Proliferation was measured by using the Cell Counting Assay Kit after cells were exposed to CsA (0 L, 10 L, 30 L, 50 L or 100 μg/mL). Apoptotic cells were identified by fluorescence microscopy of 4', 6-diamidino-2-phenylidole-stained nuclei. Western blot analysis was done for poly(ADP-ribose) polymerase (PARP), p27, p53 and caspase.
  
  
  RESULTS
  Cell viability decreased dependent on the CsA concentration. CsA treatment group showed chromatin condensation and nuclear fragmentation. CsA produced a dose-dependent induction of p27 and reduction of procasapase-3. CsA treatment induced the degradation of 116-kDa PARP into an 89-kDa fragment.
  
  
  CONCLUSIONS
  CsA induced apoptosis of endothelial cells.
authors.affiliation: Institute for Medical Science, Keimyung University, Daegu, Korea.
authors.forename: E A
authors.initials: EA
authors.lastname: Hwang
authors.forename: H S
authors.initials: HS
authors.lastname: Kim
authors.forename: E
authors.initials: E
authors.lastname: Ha
authors.forename: K C
authors.initials: KC
authors.lastname: Mun
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008856:Microscopy, Fluorescence; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C436291:CDKN1B protein, human; D007166:Immunosuppressive Agents; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016572:Cyclosporine; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3