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

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

Research output: Contribution to journalArticle

13 Citations (Scopus)

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 2008

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Thrombospondin 1
Disintegrins
Metalloproteases
Renal Dialysis
Thrombosis
Transplants
Tunica Intima
Veins
Adventitia
Western Blotting
Immunoprecipitation
Proteomics
Hyperplasia
Blood Vessels
Proteins
Macrophages
Tandem Mass Spectrometry
Reoperation
Liquid Chromatography
Isotopes

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology

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Increased Expression of A Disintegrin and Metalloproteinase Thrombospondin-1 in Thrombosed Hemodialysis Grafts. / Misra, Sanjay; Lee, Nathan; Fu, Alex A.; Raghavakaimal, Sreekumar; Mandrekar, Jayawant; Bjarnason, Haraldur; McKusick, Michael A.; Iruela-Arispe, Luisa; Mukhopadhyay, Debabrata.

In: Journal of Vascular and Interventional Radiology, Vol. 19, No. 1, 01.2008, p. 111-119.

Research output: Contribution to journalArticle

Misra, Sanjay ; Lee, Nathan ; Fu, Alex A. ; Raghavakaimal, Sreekumar ; Mandrekar, Jayawant ; Bjarnason, Haraldur ; McKusick, Michael A. ; Iruela-Arispe, Luisa ; Mukhopadhyay, Debabrata. / Increased Expression of A Disintegrin and Metalloproteinase Thrombospondin-1 in Thrombosed Hemodialysis Grafts. In: Journal of Vascular and Interventional Radiology. 2008 ; Vol. 19, No. 1. pp. 111-119.
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