Thrombomodulin (TM), a critical component of the protein C anticoagulant pathway, has previously been localized to endothelial cells (EC), but not smooth muscle cells (SMC) of the blood vessel wall. We demonstrate that cultured rat, bovine, as well as human SMC, but not blood vessel wall smooth muscle tissue, possess significant functional levels of TM and TM mRNA. Cyclic adenosine monophosphate stimulates TM expression in cultured SMC, but not EC, while tumor necrosis factor suppresses TM expression in EC but not cultured SMC. We postulate that following acute or chronic EC injury, luminal SMC can express TM, and are therefore able to protect the damaged blood vessel from thrombosis.

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