Effect of a prostaglandin I2 analog on the expression of thrombomodulin in liver and spleen endothelial cells after an extensive hepatectomy

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. 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. 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. 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.