Heme oxygenase-1 potentiates the survival of small-for-size liver graft.
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.
Yang
Zhen Fan
ZF
Centre for the Study of Liver Disease and Department of Surgery, The University of Hong Kong, Hong Kong, China.
Tsui
Tung Yu
TY
Ho
David W
DW
Tang
Terence C
TC
Fan
Sheung-Tat
ST
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
D006360:Heat-Shock Proteins; D010105:Oxygenases; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat