Effects of heme oxygenase-1 on tissue factor and thrombomodulin in the endothelial cell

Abstract

Heme oxygenases (HO) are rate-limiting enzymes that catalyze the conversion of heme into biliverdin, free iron and carbon monoxide. They exist in three different isoforms, HO-1, HO-2 and HO-3. Recently, Yachie et al. reported the first human case of HO-1 deficiency. In this child, both intravascular hemolysis and endothelial cell injury were prominent. In addition, abnormalities of coagulation/fibrinolysis system were marked. The aim of this study was to elucidate the effects of HO-1 or HO-1 products on expression of tissue factor (TF) and thrombomodulin (TM) in human endothelial cells (HUVEC), in vitro. HUVEC were incubated with either hemin (HO-1 inducer) or hemin/Tin protoporphyrin IX (SnPP, HO-1 inhibitor) at 37 °C for each hours. The levels of mRNA of HO-1, TF and TM were determined by real-time reverse transcriptase polymerase chain reaction. The levels of antigen of cell lysates were determined by ELISA. Hemin increased HO-1 and TM expression. On the other hand, hemin/SnPP increased TF expression and decreased TM expression. In conclusion, HO-1 or HO-1 products might regulate TF and TM expression and prevent thrombus formation in human endothelial cells.