title: Heme oxygenase-1 potentiates the survival of small-for-size liver graft.
abstract: This study aims to clarify the role of heme oxygenase-1 (HO-1) in small-for-size liver transplantation. Transplantation was performed using 40% small-for-size or 100% whole liver grafts in rats. When no treatment was given, over-expression of HO-1 was detected predominantly in the small-for-size grafts at 6 hours after reperfusion as compared to whole grafts in both syngeneic and allogeneic combinations. Recombinant adenoviral vector encoding HO-1 gene (AdHO-1) administered to donors 48 hours before transplantation enhanced HO-1 expression in both whole and small-for-size allografts, with a predominant augmentation in the small-for-size allografts, suggesting favorable conditions for the induction of HO-1 expression in small-for-size allografts. In close relation to the expression level of HO-1, AdHO-1 significantly prolonged both whole and small-for size allograft survivals, with a remarkable effect in the small-for-size allograft group. The prolongation of allograft survival was blocked by the HO-1 inhibitor (zinc protoprophyrin IX). The non-treated small-for-size allografts demonstrated impaired liver function during the early period after reperfusion, which could be improved by over-expression of HO-1, but reversed by the HO-1 inhibitor. The markedly increase expression HO-1 in small-for-size allografts was associated with lower levels of adhesion molecules and pro-inflammatory cytokines in the early phase after reperfusion. These findings support the beneficial effects of HO-1 on allograft survival. In conclusion, the ability of small-for-size grafts in the induction of HO-1 expression might facilitate their own survival in liver transplantation.
authors.affiliation: Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, China.
authors.forename: Zhen Fan
authors.initials: ZF
authors.lastname: Yang
authors.forename: Tung Yu
authors.initials: TY
authors.lastname: Tsui
authors.forename: David W
authors.initials: DW
authors.lastname: Ho
authors.forename: Terence C
authors.initials: TC
authors.lastname: Tang
authors.forename: Sheung-Tat
authors.initials: ST
authors.lastname: Fan
mesh_terms: D000818:Animals; D006085:Graft Survival; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing); D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D008099:Liver / Q000033:anatomy & histology* / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D016031:Liver Transplantation / Q000009:adverse effects; D009929:Organ Size; D010105:Oxygenases; D011184:Postoperative Period; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D006360:Heat-Shock Proteins; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat