Key result
Thrombin reduces endothelial thrombomodulin expression and activity by ~40%, an effect reversed by hirudin.
Why the study?
The modulation of thrombomodulin expression and activity by thrombin in human endothelial cells was not well understood.
May influence endothelial thrombogenicity; hypothesis-generating and requires in vivo confirmation before clinical relevance.
Thrombomodulin (TM) is a cell surface anticoagulant glycoprotein that plays a key role in the protein C pathway. TM expression in endothelial cells may be modulated by a variety of extracellular signals. Most notably, TM has been shown to be downregulated by inflammatory mediators, such as tumor necrosis factor-alpha and lipopolysaccharide. The objective of this study was to determine the effect of thrombin on TM expression and activity. Thrombin resulted in reduced TM in primary cultures of human endothelial cells by approximately 40% at the level of mRNA, protein, and activity. These effects were blocked by the thrombin inhibitor hirudin. These results suggest that activation of the coagulation cascade may result in a positive-feedback loop consisting of thrombin-mediated repression of TM-dependent protein C activation.
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Séguin et al. (2008) studied this question. Thrombin was evaluated on Thrombomodulin (TM) expression and activity. Thrombin reduced thrombomodulin expression and activity in primary human endothelial cells by approximately 40%, an effect that was blocked by the thrombin inhibitor hirudin.
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