Increased Expression of A Disintegrin and Metalloproteinase Thrombospondin-1 in Thrombosed Hemodialysis Grafts

Sanjay Misra, Nathan Lee, Alex A. Fu, Sreekumar Raghavakaimal, Jaywant Mandrekar, Haraldur Bjarnason, Michael A. McKusick, Luisa Iruela-Arispe, Debabrata Mukhopadhyay

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Abstract

Purpose: To use proteomic analysis to identify upregulated and downregulated proteins in thrombosed hemodialysis graft specimens. One of these significantly upregulated proteins was a disintegrin and metalloproteinase thrombospondin-1 (ADAMTS-1), and its expression and activity were determined in thrombosed hemodialysis grafts. Materials and Methods: Hemodialysis vascular access samples (thrombosed veins, n = 8; control veins, n = 6) were obtained from patients who required surgical revision. Proteomic analysis was performed with isotope-coded affinity tag labeling with multidimensional liquid chromatography followed by tandem mass spectrometry on four thrombosed hemodialysis graft specimens with control veins. Expression of ADAMTS-1 was confirmed by performing immunoprecipitation followed by Western blot analysis. Finally, immunohistochemistry was used to localize expression in a separate group of patients with thrombosed grafts. Results: Thirty-nine unique proteins were common to all four patients. ADAMTS-1 was one of the only significantly upregulated protein (>38 fold). ADAMTS-1 expression was confirmed by performing immunoprecipitation and Western blot analysis and was significantly increased. ADAMTS-1 expression was localized to adventitial macrophages and neutrophils of thrombosed grafts. Conclusions: ADAMTS-1 was significantly upregulated in thrombosed hemodialysis grafts by mass spectrometric analysis and Western blot analysis. Expression was localized to adventitial macrophages and leukocytes. It is hypothesized that ADAMTS-1 may be related to intimal hyperplasia in hemodialysis vascular access grafts. Future work is planned on inhibiting ADAMTS-1 expression and determining the effect on intimal hyperplasia in hemodialysis grafts.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalJournal of Vascular and Interventional Radiology
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2008

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ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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