It had been shown that statins act on endothelial cells, as described by Mussoni et al., uvastatin inhibits the activity of plasminogen activator inhibitor and induces the release of tissue plasminogen activator indicating a marked improvement in the brinolytic route. The truth is, the inhibition of HMG CoA reductase by statins leads to a decreased synthesis of cholesterol and also its precursors, which are isoprenoid products of mevalonate. These farnesylpyrophosphate, isoprenoids and geranylgeranylpyrophosphate, order Crizotinib provide lipophilic anchors which are required for membrane attachment and biological action of small GTP binding protein from the Ras family. For applying their function in cell signal transduction, protein Ras and RhoA of the GTPase family must translocate from the cytoplasm to the cell membrane. This translocation needs FPP for GGPP and Ras for RhoA. Activation of Ras is involved in the activation of mitogen activated protein kinase and nuclear factor kappa B pathways which may play an essential role in angiogenesis. Triggered RhoA is known to keep company with cortical actin in focal contact internet sites at cell membrane ru es, and thus is a must for the corporation of actin cytoskeleton and as effect for cell locomotion which is of primary importance in angiogenesis. Moreover, using the exoenzyme, clostridium botulinum C3 transferase, which speci cally Metastatic carcinoma prevents the activation of Rho GTPase, inhibits angiogenesis in vitro and in vivo. Since cerivastatin prevents FPP and GGPP biosynthesis by inhibiting HMG CoA reductase, we were motivated to analyze the result of such inhibition on endothelial cell migration and angiogenesis. In this study, we show that cerivastatin inhibits the migration of endothelial cells and the capillary tube development stimulated by angiogenic factors, i. e. bFGF, OSM and VEGF. We tested OSM in addition to well known angiogenic facets since this in ammatory cytokine is largely expressed in-the atheromatous plaque. We also examined the molecular mechanism of such inhibition related specially to natural product libraries Ras and RhoA inhibition. RpD Systems offered VEGF, recombinant human OSM and bFGF. Cerivastatin was kindly given by Bayer Pharma. The HMEC 1 cell line was given by Dr. Ades. HMEC 1 were cultured in MCDB 131 medium, supplemented with 100 IU/ml penicillin, fifteen minutes fetal calf serum, 100 Wg/ml streptomycin, 10 ng/ml epidermal growth factor and 1 mg/ml hydrocortisone. HMEC 1 were detached with EDTA 0. 5 mM, washed twice in phosphate bu ered saline and resuspended in MCDB 131 medium with 0. 2 mg/ml bovine serum albumin. 50U103 cells were seeded in the upper chamber of a transwell insert. The lower chamber was lled with 1 ml of MCDB 131 with 2 mg/ml of BSA without o-r with angiogenic factors used at indicated levels.