Effect of a prostaglandin I ₂ analog on the expression of thrombomodulin in liver and spleen endothelial cells after an extensive hepatectomy

Purpose: Dysfunction of the remnant liver after a hepatectomy is caused by microthrombus formation due to endothelial cell (EC) damage. This study evaluated the effect of prostaglandin I ₂ (PGI ₂) on the expression of thrombomodulin (TM), a marker for the anticoagulant properties of ECs, using cultured human umbilical vein endothelial cells (HUVECs), and using a canine extensive hepatectomy model. Methods: The presence of PGI ₂ receptors was confirmed on HUVECs by reverse transcription-polymerase chain reaction, and the effect of the PGI ₂ analog on TM expression on HUVECs was determined by an enzyme-linked immunosorbent assay. Twenty mongrel dogs were divided into four groups comprising a sham operation, 70% hepatectomy, 84% hepatectomy, and 84% hepatectomy, with the administration of the PGI ₂ analog, respectively, and TM expression in the liver, spleen, pancreas, kidney, lung, portal vein, and intestine was determined immunohistochemically. Results: The TM expression on HUVECs was upregulated by the PGI ₂ analog. The TM expression on ECs in the hepatic sinusoids and splenic sinus were markedly decreased after the 84% hepatectomy, but such damage was markedly mitigated following an 84% hepatectomy with administration of the PGI ₂ analog. Conclusions: An extensive hepatectomy induced severe EC damage not only in the hepatic sinusoids but in the splenic sinuses as well. Prostaglandin I ₂ prevented damage to these ECs, suggesting that PGI ₂ improves the microcirculation in the remnant liver.