Prostaglandin E1 Protects Human Liver Sinusoidal Endothelial Cell from Apoptosis Induced by Hypoxia Reoxygenation

Abstract

Hepatic ischemia-reperfusion injury is an important cause of graft dysfunction after liver transplantation. Liver sinusoidal endothelial cells (LSECs) are particularly sensitive to ischemia-reperfusion injury and undergo apoptosis. This study investigates the protective role of PGE1 on apoptosis of LSEC during hypoxia-reoxygenation in vitro. Hypothermia-hypoxia followed by reoxygenation triggered LSEC apoptosis, and prostaglandin PGE1 protected LSEC from apoptosis in a dose-dependent manner. The release of matrix metalloproteinases (MMPs) and nitric oxide (NO) by LSECs were increased after hypoxia reoxygenation. Both the MMP inhibitor BB3103 and the NO inhibitor LNAM effectively decreased LSEC apoptosis, suggesting a separate role of MMPs and NO in hypoxia-reoxygenation-induced LSEC apoptosis. PGE1 down-regulated NO production by inhibiting the expression of inducible NO synthase in LSEC. PGE1 also inhibited MMP-2 release from LSEC during hypoxia reoxygenation. These results indicate that the protection of LSECs from apoptosis by PGE1 in hepatic ischemia-reperfusion injury is mediated by inhibiting inducible NO synthase and MMP release.