RhoA/ROCK signaling is essential for multiple aspects of VEGF-mediated angiogenesis.

ABSTRACT: The small GTPase RhoA and its downstream effectors, ROCK1 and ROCK2, regulate a number of cellular processes, including cell motility, proliferation, survival, and permeability. Pharmacological inhibitors of the Rho pathway reportedly block angiogenesis; however, the molecular details of this inhibition are largely unknown. We demonstrate that vascular endothelial growth factor-A (VEGF) rapidly induces RhoA activation in endothelial cells (ECs). Moreover, the pharmacological inhibition of ROCK1/2 using 10 microM Y-27632 (the IC(50) for this compound in ECs) strongly disrupts vasculogenesis in pluripotent embryonic stem cell cultures, VEGF-mediated regenerative angiogenesis in ex vivo retinal explants, and VEGF-mediated in vitro EC tube formation. Furthermore, using small interfering RNA kn

SUBMITTER: Bryan BA 

PROVIDER: S-EPMC2923346 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature