Modulation of coagulation and fibrinolytic pathways by statins.

Activation of the coagulation pathway and the inhibition of the fibrinolytic pathway play a pivotal role in the pathogenesis of thrombotic vascular disease such as acute coronary syndromes. Statins have been proved to be effective in patients with acute coronary syndromes in terms of reduction of cardiovascular events. It is assumed that the direct effects on vascular cells, which are independent of lipid-lowering, particularly the alterations in coagulation and fibrinolytic pathways, may contribute to these benefits. Indeed, in endothelial cells and vascular smooth muscle cells as well as in monocytes/macrophages, stains reduce tissue factor and plasminogen activator-1 expression and activity and increase tissue plasminogen activator expression and activity. These effects are mainly mediated by the inhibition of the Rho pathway, whereas the activation of Akt by statins plays a role in the suppression of tissue factor expression. These effects on coagulation and fibrinolytic pathways may be particularly important in patients with acute coronary syndromes.