Thrombomodulin as a marker of endothelium damage in some clinical conditions

Abstract

Background: Thrombomodulin (TM) is a membrane glycoprotein in the vascular endothelium. It may be cleaved from endothelial cells and released into the circulation. The plasma TM level depends on the integrity of the endothelium and the clearance of the molecule. The physiological role of soluble TM forms is still unclear. The clinical significance of elevated levels of TM in various pathologic conditions is not well established yet. To analyze variations of plasma TM level in different clinical situations, its concentrations in patients with three groups of diseases were measured and compared with those in healthy subjects. Methods: Plasma samples from 23 patients at risk for development of vascular complications [essential hypertension (EH), stages 1 and 2], 31 patients with inflammatory bowel diseases [Crohn’s disease (IBD), mostly in the active stage], and 19 patients with malignant tumors [gastric carcinoma (NEO)], were analyzed for soluble TM with an enzyme immunoassay kit. Results: In the group of patients with the early stages of EH and with non-active IBD, no significant changes were found in comparison to the healthy subjects. In the patients with active IBD and mainly with NEO, soluble TM was significantly increased ( P<0.05 and P<0.001, respectively). Conclusions: Our TM levels failed to demonstrate increased endothelial damage in the early stage of EH. This suggests that TM is released into the plasma only by true endothelial cell damage during the development of vascular complications. Probably a certain degree of endothelial injury is necessary for an increase in plasma. In the active stage of IBD and in NEO, soluble TM appears to be derived not only from injured endothelial cells, but may also be proteolytically cleaved from membrane TM by proteases. There may also be increased synthesis of TM in activated and/or transformed cells.