FIGURE 1. Effects of the inhibition of HMG-CoA reductase by statins. By blocking cholesterol biosynthesis, HMG-CoA reductase inhibitors or statins also decrease the synthesis of key isoprenoid intermediates such as farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP). GGPP mediates the isoprenylation or geranylgeranylation of Rho proteins, a critical step in the translocation of Rho proteins from the cytoplasm to the plasma membrane where they initiate downstream signaling via Rho-Kinase. The activation of Rho proteins by GGPP is an important signaling event in fibrinolysis by modulating tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels. Exoenzyme C3 transferase (C3 transferase) selectively blocks RhoA/B/C signaling. Adapted from Budzyn et al.²³