Fig. 8.

Simplified schematics of the molecular changes for RhoA prenylation leading to RhoA/ROCK activation responsible for the basal tone in the IAS. HMG-CoA reductase exerts upstream regulation of RhoA prenylation via geranylgeranyltransferase I (GGTase I). The latter catalyzes the covalent attachment of the geranylgeranyl group from GGPP to RhoA (RhoA prenylation). RhoA prenylation plays an important role in the translocation of RhoA to the membrane followed by the activation of RhoA/ROCK. Data show that simvastatin blocks this upstream regulation of RhoA prenylation/RhoA/ROCK pathways, thus causing a decrease in the basal IAS tone, as well as its increase by thromboxane A₂ (TXA₂) analog U-46619. MLCP, myosin light-chain phosphatase.