Gene transfer of heme oxygenase-1 and carbon monoxide delivery inhibit chronic rejection

Am J Transplant. 2002 Aug;2(7):581-92. doi: 10.1034/j.1600-6143.2002.20702.x.


The hallmark of chronic rejection is the occlusion of the artery lumen by intima hyperplasia as a consequence of leukocyte infiltration and vascular smooth muscle cell (VSMC) migration and proliferation. Heme oxygenase-1 (HO-1) is a tissue protective molecule which degrades heme into carbon monoxide (CO), free iron and biliverdin. We analyzed the effects of HO-1 gene transfer into the vessel wall using an adenoviral vector (AdHO-1) and of CO delivery in a model of chronic allogeneic aorta rejection in rats. Carbon monoxide treatment was achieved by a new pharmacological approach in transplantation using methylene chloride (MC), which releases CO after degradation. AdHO-1-mediated gene transfer into aorta endothelial cells (ECs) or CO delivery resulted in a significant reduction in intimal thickness compared to untreated or noncoding adenovirus-treated controls. Aortas transduced with AdHO-1 or treated with CO showed a reduction in the number of leukocytes as well as in the expression of adhesion molecules, costimulatory molecules and cytokines, with the gene transfer treatment displaying a more pronounced effect than the CO treatment. Conversely, CO inhibited VSMC accumulation in the intima more efficiently than AdHO-1 treatment. Gene transfer of HO-1 and pharmacological manipulation of CO are novel approaches to the analysis and treatment of chronic rejection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells / transplantation
  • Carbon Monoxide / therapeutic use*
  • Carboxyhemoglobin / pharmacokinetics
  • Chlorocebus aethiops
  • Chronic Disease
  • Gene Transfer Techniques
  • Graft Rejection / prevention & control*
  • Heme Oxygenase (Decyclizing) / genetics*
  • Heme Oxygenase (Decyclizing) / metabolism
  • Heme Oxygenase-1
  • Male
  • Rats
  • Rats, Inbred Lew
  • Transplantation, Heterologous
  • Transplantation, Homologous
  • Transplantation, Isogeneic


  • Carbon Monoxide
  • Carboxyhemoglobin
  • Heme Oxygenase (Decyclizing)
  • Heme Oxygenase-1