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)
JournalAmerican Journal of Physiology - Renal Physiology
Volume305
Issue number4
DOIs
StatePublished - May 8 2013

Fingerprint

Heme Oxygenase (Decyclizing)
Arteriovenous Fistula
Carotid Arteries
Blood Vessels
heme oxygenase-2
Vasodilator Agents
Endothelium
Messenger RNA
Uremia
Matrix Metalloproteinase 2
Jugular Veins
Matrix Metalloproteinase 9
Carbon Monoxide
Nephrectomy
Heme

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

@article{ea8bd941f9e544109eaaa4234d05dc55,
title = "Functioning of an arteriovenous fistula requires heme oxygenase",
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.",
keywords = "Arteriovenous fistula, Heme oxygenase-2, Hemodialysis, Vascular access",
author = "Lu Kang and Grande, {Joseph Peter} and Gianrico Farrugia and Croatt, {Anthony J.} and Katusic, {Zvonimir S} and Nath, {Karl A}",
year = "2013",
month = "5",
day = "8",
doi = "10.1152/ajprenal.00234.2013",
language = "English (US)",
volume = "305",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
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T1 - Functioning of an arteriovenous fistula requires heme oxygenase

AU - Kang, Lu

AU - Grande, Joseph Peter

AU - Farrugia, Gianrico

AU - Croatt, Anthony J.

AU - Katusic, Zvonimir S

AU - Nath, Karl A

PY - 2013/5/8

Y1 - 2013/5/8

N2 - 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.

AB - 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.

KW - Arteriovenous fistula

KW - Heme oxygenase-2

KW - Hemodialysis

KW - Vascular access

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U2 - 10.1152/ajprenal.00234.2013

DO - 10.1152/ajprenal.00234.2013

M3 - Article

C2 - 23678042

AN - SCOPUS:84881624070

VL - 305

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

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