title: Nucleotide metabolic mismatches in mammalian hearts: implications for transplantation.
abstract: BACKGROUND
  Human donor organ shortages have led surgeons and scientists to explore the use of animals as alternative organ sources. Acute thrombovascular rejection (AVR) is the main hurdle in xenotransplantation. disparities in nucleotide metabolism in the vessels of different species  may contribute significantly to the microvascular component of AVR.
  
  
  METHODS
  We evaluated the extent of nucleotide metabolism mismatch in selected organs and endothelial cells of different mammals with particular focus on the changes in activity of ecto-5'-nucleotidase (E5'n) elicited  by exposure of porcine hearts or endothelial cells to human blood (ex vivo) or human plasma (in vitro).
  
  
  RESULTS
  E5'n activity in the rat heart was significantly higher than in other species. We noted a significant difference (p<0.001) in E5'n activity between human and pig endothelial  cell lines. Initial pig aortic endothelial E5'n activity decreased in vitro after a three-hour exposure to human and porcine plasma while remaining constant in controls. ex vivo perfusion with fresh human blood for four hours resulted in a significant decrease of E5'n activity in both wild  type and transgenic pig hearts overexpressing human decay accelerating factor (p<0.001).
  
  
  CONCLUSIONS
  This study provides evidence that mismatches in basal mammalian metabolic pathways and humoral immunity interact in a xenogeneic environment. understanding the role of nucleotide  metabolism and signalling in xenotransplantation may identify new targets for genetic modifications and may lead to the development of new therapies extending graft survival.
authors: Division of Cardiothoracic Surgery, University of Arizona College of Medicine, 1,501 North Campbell Avenue, PO Box 245071, Tucson, AZ 85724-5071, USA. zkhalpey@surgery.arizona.edu
authors: Z
authors: Z
authors: Khalpey
authors: M H
authors: MH
authors: Yacoub
authors: R T
authors: RT
authors: Smolenski
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001769:Blood; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D006085:Graft Survival; D006801:Humans; D056724:Immunity, Humoral / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D010215:Papio; D011687:Purines / Q000378:metabolism; D011743:Pyrimidines / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D034421:Sus scrofa; D013552:Swine; D014183:Transplantation, Heterologous
chemical_list: D011687:Purines; D011743:Pyrimidines; D015720:5'-Nucleotidase