Functioning of an arteriovenous fistula requires heme oxygenase

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Abstract

Heme oxygenase-2 (HO-2), the constitutive isoform of the heme-degrading enzyme heme oxygenase, may serve as an anti-inflammatory vasorelaxant, in part, by generating carbon monoxide. Arteriovenous fistulas (AVFs) are employed as hemodialysis vascular accesses because they provide an accessible, high-blood-flow vascular segment. We examined the role of vascular expression of HO-2 in AVF function. An AVF was created in mice by anastomosing the carotid artery to the jugular vein. HO-2 expression was detected by immunohistochemistry in the intact carotid artery, mainly in endothelial cells and smooth muscle cells; expression of HO-2 protein and mRNA was modestly increased in the artery of the AVF. Creating an AVF in HO-2-/- mice compared with an AVF in HO-2+/+ mice led to markedly reduced AVF blood flow and increased numbers of nonfunctioning AVFs. The impairment of AVF function in the setting of HO-2 deficiency could not be ascribed to either preexisting intrinsic abnormalities in endothelium- dependent and endothelium-independent relaxation of the carotid artery in HO-2-deficient mice or to impaired vasorelaxant responses in the intact carotid artery in vivo. HO-1 mRNA was comparably induced in the AVF in HO-2+/+ and HO-2-/- mice, whereas the AVF in HO-2-/- mice compared with that in HO-2+/+ mice exhibited exaggerated induction of matrix metalloproteinase (MMP)-9 but similar induction of MMP-2. HO-2 deficiency also led to lower AVF blood flow when AVFs were created in uremia, the latter induced by subtotal nephrectomy. We conclude that HO-2 critically contributes to the adequacy of AVF blood flow and function.

Original languageEnglish (US)
Pages (from-to)F545F-F552
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number4
DOIs
StatePublished - May 8 2013

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Keywords

  • Arteriovenous fistula
  • Heme oxygenase-2
  • Hemodialysis
  • Vascular access

ASJC Scopus subject areas

  • Physiology
  • Urology

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