Apoptosis and regeneration of sinusoidal endothelial cells after extended cold preservation and transplantation of rat liver.
BACKGROUND
Sinusoidal endothelial cells (SECs) are particularly susceptible to cold ischemia-reperfusion (I/R) injury. We have examined the process of injury and recovery of graft after cold-preserved liver transplantation, with special focus on the proliferation of SECs and regulatory mechanisms involved.


METHODS
Male SD rats were divided into two groups according to length of cold preservation time in University of Wisconsin [UW] solution of graft: UW1h group and UW12h group. Graft function, incidence of apoptosis, proliferation of SECs and the expression of related regulatory factors were assessed after orthotopic liver transplantation (OLT).


RESULTS
SECs are more sensitive to apoptosis induced by cold I/R injury compared with hepatocytes. Using bromodeoxyuridine and rat endothelial cell antigen-1 double immunostaining assay, SECs exhibited a delayed proliferation in comparison with hepatocytes, reaching a peak at 72 hr in UW1h group and 96 hr in UW12h group, respectively. Vascular endothelial growth factor increased at 24 hr after reperfusion, and peaked at 72 hr in both groups. Flt-1 and flk-1 expression was found to be mainly limited to SECs, with a peak in expression occurring between 72 and 96 hr, which coincided with the peak in SEC proliferation in UW1h group. However, flt-1 was found to be reduced significantly at any time throughout the experiments in UW12h group compared to sham.


CONCLUSIONS
The delayed recovery of rat liver after extended cold preservation and transplantation correlates with a retarded regeneration of SECs due to increased apoptosis and reduced expression of flt-1. These results suggest that SECs play an important role in cold-preserved liver transplantation.
Zhu
Jin
J
Southwest Hospital & Institute of Hepatobiliary Surgery, Key Laboratory of Liver Transplantation, P.L.A., Third Military Medical University, Chongqing, P.R. China.
Wang
Shuguang
S
Bie
Ping
P
Li
Xiaowu
X
Zhang
Yujun
Y
Xiong
Yan
Y
Wang
Huaizhi
H
Ma
Zhengwei
Z
Li
Kun
K
Dong
Jiahong
J
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D003080:Cold Temperature; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology* / Q000201:enzymology; D006820:Hyaluronic Acid / Q000097:blood; D008099:Liver / Q000502:physiology*; D008115:Liver Regeneration; D016031:Liver Transplantation; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology; D015996:Survival Rate; D013997:Time Factors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics
D012333:RNA, Messenger; D006820:Hyaluronic Acid; D000410:Alanine Transaminase; C501163:Flt1 protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D053148:Caspase 3