Thrombin in arterial thrombosis

Thrombin plays a pivotal role in the pathogenesis of arterial thrombosis. Platelet-rich thrombosis after arterial injury is dependent on the depth and extent of injury, local rheological conditions and the persistence of residual mural thrombus. The unique effects of specific thrombin inhibitors, including thrombin action on platelets and blood coagulation, demonstrated in experimental and preliminary clinical trials, suggest that specific thrombin inhibitors may be the next major advance in antithrombotic therapy of acute coronary syndromes. The importance of thrombin lies not just in acute thrombus formation following arterial injury but thrombin also contributes to smooth muscle cell proliferation by stimulating platelet secretion of growth factors (especially platelet derived growth factor, PDGF) and directly acting on smooth muscle cells. Thus, thrombin has direct effects on cell proliferation and influences the cellular synthetic mechanisms responsible for matrix protein and collagen production. The role for thrombin as a possible mitogen for vascular cells has gained support by the identification of a cellular thrombin receptor and by the recent detection of m-RNA for this receptor in human atherosclerotic plaques. Therefore, specific thrombin inhibition may also have a potential impact on the relative proliferative response of endothelial and smooth muscle cells after arterial injury such as PTCA by preventing restenosis.