American Journal of Kidney Diseases
Volume 51, Issue 4 , Pages 603-612, April 2008

Differential Expression of Proteins From Cultured Endothelial Cells Exposed to Uremic Versus Normal Serum

  • Carla Carbó

      Affiliations

    • Servicio de Hemoterapia-Hemostasia y, Centre de Diagnòstic Biomèdic, Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  • ,
  • Gemma Arderiu, PhD

      Affiliations

    • Servicio de Hemoterapia-Hemostasia y, Centre de Diagnòstic Biomèdic, Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  • ,
  • Ginés Escolar, MD, PhD

      Affiliations

    • Servicio de Hemoterapia-Hemostasia y, Centre de Diagnòstic Biomèdic, Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  • ,
  • Berta Fusté, PhD

      Affiliations

    • Servicio de Hemoterapia-Hemostasia y, Centre de Diagnòstic Biomèdic, Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  • ,
  • Aleix Cases, MD, PhD

      Affiliations

    • Servicio de Nefrología, Centre de Diagnòstic Biomèdic, Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
  • ,
  • Montserrat Carrascal, PhD

      Affiliations

    • Centro Superior de Investigaciones Científicas–Universidad Autónoma de Barcelona (CSIC-UAB) Proteomics Facility, Instituto de Investigaciones Biomédicas de Barcelona-CSIC/IDIBAPS, Barcelona, Spain.
  • ,
  • Joaquín Abián, PhD

      Affiliations

    • Centro Superior de Investigaciones Científicas–Universidad Autónoma de Barcelona (CSIC-UAB) Proteomics Facility, Instituto de Investigaciones Biomédicas de Barcelona-CSIC/IDIBAPS, Barcelona, Spain.
  • ,
  • Maribel Díaz-Ricart, PhD

      Affiliations

    • Servicio de Hemoterapia-Hemostasia y, Centre de Diagnòstic Biomèdic, Institut d’Investigacions biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain
    • Corresponding Author InformationAddress correspondence to Maribel Díaz-Ricart, PhD, Servicio de Hemoterapia-Hemostasia, Hospital Clínic, Villarroel 170, 08036 Barcelona, Spain.

Received 24 May 2007; accepted 28 November 2007.

Background

Deficient hemostasis and accelerated atherosclerosis coexist in patients with chronic kidney disease. Endothelial dysfunction may be involved in the high incidence of atherothrombotic events in these patients. We established an in vitro model of endothelial dysfunction by exposing endothelial cells to uremic media and applied a proteomic approach to characterize endothelial cell dysfunction in uremia.

Study Design

Cross-sectional study.

Setting and Participants

Serum samples from 8 patients with chronic kidney disease on hemodialysis treatment were collected.

Predictor

Exposure of cultured endothelial cells to normal and uremic serum.

Outcome and Measurements

Proteins from lysed cells were characterized by isoelectric point and molecular weight by using 2-dimensional gel electrophoresis. Spots were visualized by means of silver staining and identified by using mass spectrometry.

Results

Identification of the most prominent proteins showed molecules related to inflammation (high mobility group box 1, aldose reductase, and proteasome components) and oxidative stress (superoxide dismutase and glutathione peroxidase), both associated with chronic kidney disease. These changes may be caused by activation of the nuclear factor-κB transcription factor. Changes in expression of cytoskeletal proteins (destrin and vimentin) also were detected.

Limitations

In vitro study.

Conclusion

Proteomic techniques proved to be a powerful tool to investigate endothelial dysfunction in uremia. A more exhaustive analysis will provide answers and potential therapeutic targets in the near future.

Index Words: Endothelial dysfunction, uremia, inflammation, oxidative stress, proteomics, SOD

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PII: S0272-6386(08)00031-0

doi:10.1053/j.ajkd.2007.11.029

American Journal of Kidney Diseases
Volume 51, Issue 4 , Pages 603-612, April 2008