Carbon monoxide ameliorates renal cold ischemia-reperfusion injury with an upregulation of vascular endothelial growth factor by activation of hypoxia-inducible factor. Academic Article uri icon

Overview

MeSH

  • Administration, Inhalation
  • Animals
  • Dose-Response Relationship, Drug
  • Endothelin-1
  • Male
  • Nitric Oxide
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Rats
  • Rats, Inbred Lew
  • Receptors, Endothelin
  • Up-Regulation

MeSH Major

  • Carbon Monoxide
  • Cold Ischemia
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Kidney
  • Kidney Transplantation
  • Reperfusion Injury
  • Vascular Endothelial Growth Factor A

abstract

  • We have previously shown that carbon monoxide (CO) inhalation at a low concentration provides protection against cold ischemia-reperfusion (I/R) injury after kidney transplantation. As vascular endothelial growth factor (VEGF) may promote the recovery process of impaired vascular endothelial cells during I/R injury, we examined whether protective effects of CO involved VEGF induction and its upstream hypoxia-inducible factor (HIF)-1 activation. Lewis rat kidney graft, preserved in University of Wisconsin at 4 degrees C for 24 hr, was orthotopically transplanted into syngeneic recipient. Recipients were continuously maintained in air or exposed to CO (250 ppm) for 1 hr before and 24 hr after transplant. Prolonged cold preservation resulted in progressive impairment of kidney graft function with early inflammatory responses. Carbon monoxide significantly protected kidney grafts from cold I/R injury, improved renal function and enhanced recipient survival. Real-time reverse transcriptase-polymerase chain reaction revealed upregulation of HIF-1alpha and VEGF in the CO-treated kidney grafts as early as 1 hr after reperfusion. Western blot showed CO significantly upregulated VEGF expression 1 to 3 hr after kidney transplantation. Considerably more VEGF-positive cells were observed mainly in tubular epithelial cells in CO-treated, but not air-exposed, kidney grafts at 3 hr after reperfusion. YC-1, HIF-1alpha inhibitor, completely abrogated the actions of CO on VEGF induction and reversed the protective effects afforded by CO. Nitric oxide production in the grafts was increased by CO, however, abolished by YC-1. These results demonstrate that the protective effect of CO against renal cold I/R injury may involve VEGF upregulation through its upstream signal, HIF-1 activation.

publication date

  • June 27, 2008

has subject area

  • Administration, Inhalation
  • Animals
  • Carbon Monoxide
  • Cold Ischemia
  • Dose-Response Relationship, Drug
  • Endothelin-1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Kidney
  • Kidney Transplantation
  • Male
  • Nitric Oxide
  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Rats
  • Rats, Inbred Lew
  • Receptors, Endothelin
  • Reperfusion Injury
  • Up-Regulation
  • Vascular Endothelial Growth Factor A

Research

keywords

  • Journal Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1097/TP.0b013e31817c6f63

PubMed ID

  • 18580478

Additional Document Info

start page

  • 1833

end page

  • 1840

volume

  • 85

number

  • 12