Adventitial remodeling with increased matrix metalloproteinase-2 activity in a porcine arteriovenous polytetrafluoroethylene grafts

Sanjay Misra, Michael G. Doherty, David Woodrum, Jay Homburger, Jaywant N. Mandrekar, Stephane Elkouri, Enrique A. Sabater, Haraldur Bjarnason, Alex A. Fu, James F. Glockner, Eddie L. Greene, Debabrata Mukhopadhyay

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Background. We hypothesized the source of early proliferating cells contributing to venous stenosis formation in a porcine hemodialysis grafts is the adventitia and media, and migration of these cells is greatest within the first two weeks following graft placement, resulting in increased matrix metalloproteinase-2 (MMP-2) activity. Methods. Polytetrafluoroethylene grafts from the iliac artery to the ipsilateral iliac vein were placed in 23 pigs and 5-Bromo-2′-deoxyuridine (BrdU) was given at 24 and 48 hours after surgery to assess cell proliferation and migration. Angiography and magnetic resonance angiography was performed. Animals were euthanized on day three (N = 6), day seven, (N = 5), day 14 (N = 6), and days 19 to 26 (N = 6) after graft placement, and stenotic tissue and unaffected contralateral iliac vein were removed for zymography and immunostaining. Results. Migration of cells derived from the adventitia and media peaked at day 14. Adventitial diameter of the stenotic vein decreased, while the intima to media ratio increased. MMP-2 activity peaks at day seven in the adventitia and days 19 to 26 in the intima. Conclusion. These results confirm our hypothesis that the source of cells resulting in venous stenosis formation is derived from the adventitia and media, with cell migration being greatest within the first two weeks after graft placement with translocation of these cells into the intima at four weeks. MMP-2 activity peaks at day seven in the adventitia and again at days 19 to 26 in the intima. A key to limiting venous stenosis formation may lie in inhibiting MMP-2 by adventitial and medial targeting.

Original languageEnglish (US)
Pages (from-to)2890-2900
Number of pages11
JournalKidney international
Volume68
Issue number6
DOIs
StatePublished - Dec 1 2005

Keywords

  • Cell migration
  • Dialysis access
  • Intimal hyperplasia
  • Stenosis

ASJC Scopus subject areas

  • Nephrology

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