Adenovirus-mediated overexpression of glutathione-s-transferase mitigates transplant arteriosclerosis in rabbit carotid allografts

Ya Xu, Bin Gong, Yongzhen Yang, Yogesh C. Awasthi, Paul J. Boor

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background: Cardiac transplant arteriosclerosis or cardiac allograft vasculopathy remains the leading cause of graft failure and patient death in heart transplant recipients. Endothelial cell injury is crucial in the development of human atherosclerosis and may play a role in allograft vasculopathy. Glutathione-S-transferase (GST) is known to protect endothelial cells from damage by oxidants and toxins. However, the contribution of human GST A4-4 (hGSTA4-4) to vascular cell injury and consequent transplant arteriosclerosis is unknown. Methods: A recombinant adenoviral vector containing hGSTA4-4 gene was constructed and delivered to vascular endothelial cells in an in vivo rabbit carotid artery transplant model. Forty-five days after transplantation, allografts were harvested (n=28). Blood flow was measured by ultrasonography. In addition, grafts were analyzed by histology, morphometry, immunostaining, and western blot. Results: The severity of arteriosclerosis in hGSTA4-4 transduced allografts was compared with control by measuring degree of stenosis by neointima. Decrease in blood flow in hGSTA4-4 transduced allografts was significantly less than control allografts, which also developed greater intimal thickening and stenosis than hGSTA4-4 transduced allografts in the proximal and distal regions of the graft. Leukocyte and macrophage infiltration was reduced in hGSTA4-4 transduced carotid arteries. Conclusion: Our data indicate that hGSTA4-4 overexpression protects the integrity of vessel wall from oxidative injury, and attenuates transplant arteriosclerosis.

Original languageEnglish (US)
Pages (from-to)409-416
Number of pages8
JournalTransplantation
Volume89
Issue number4
DOIs
StatePublished - Feb 2010

Keywords

  • Allograft
  • Glutathione-S-transferase
  • Neointima
  • Transplant arteriosclerosis

ASJC Scopus subject areas

  • Transplantation

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