Genetic deficiency of heme oxygenase-1 impairs functionality and form of an arteriovenous fistula in the mouse

Kidney Int. 2008 Jul;74(1):47-51. doi: 10.1038/ki.2008.110. Epub 2008 Mar 26.


Vascular access dysfunction contributes to patient morbidity during maintenance hemodialysis. In this study we determined if knockout of heme oxygenase-1 predisposed to malfunction of arteriovenous fistulas. After three weeks, all fistulas in wild type mice were patent whereas a third of the fistulas in knockout mice were occluded and these exhibited increased neointimal hyperplasia and venous wall thickening. Heme oxygenase-1 mRNA and protein were robustly induced in the fistulas of the wild type mice. In the knockout mice there was increased PAI-1 and MCP-1 expression, marked induction of MMP-2 and MMP-9, but similar expression of PDGF alpha, IGF-1, TGF-beta1, VEGF, and osteopontin compared to wild type mice. We conclude that heme oxygenase-1 deficiency promotes vasculopathic gene expression, accelerates neointimal hyperplasia and impairs the function of arteriovenous fistulas.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Arteriovenous Shunt, Surgical
  • Blood Vessels / injuries
  • Blood Vessels / pathology
  • Catheters, Indwelling / adverse effects*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Heme Oxygenase-1 / deficiency*
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / physiology
  • Mice
  • Mice, Knockout
  • Tunica Intima / pathology


  • Heme Oxygenase-1