The suppression of small GTPase Rho signal transduction pathway inhibits angiogenesis in vitro and in vivo

Angiogenesis consists of multistep pathways such as the degradation of the matrix, proliferation of the endothelial cells, motility of the endothelial cells, formation of the cord structure and network formation of microvesse ls. The small GTPase Rho participates in cell motility through actin fiber polymerization. The role of the small GTPase Rho signal transduction pathwa y in regulating angiogenesis, however, is still unknown. In this study, we investigated the role of the small GTPase Rho signal transduction pathway i n angiogenesis in vitro and in vivo using the exoenzyme, Clostridium botuli num C3 transferase, which specifically suppresses Rho and a compound, Y-276 32, which suppresses p160ROCK (Rho-associated coiled-coil containing protei n kinase). In this paper, we showed that the small GTPase Rho-p160ROCK sign al transduction pathway played an important role in angiogenesis both in vi tro and in vivo. These results suggest that inhibition of the small GTPase Rho signal transduction pathway by the p160ROCK inhibitor could be a possib le new strategy for angiogenic diseases. (C) 2000 Academic Press.