title: Rac1 regulates cardiovascular development and postnatal function of endothelium.
abstract: Rac1 is a member of the small Rho GTPase family, which controls actin cytoskeleton and focal adhesion dynamics in cellular protrusions. While Rac1 therefore contributes to regulation of endothelial cell-cell and cell-matrix interactions, a detailed understanding of its role in endothelium function is lacking. Recently, the role of Rac1 in development and postnatal regulation of the cardiovascular system has been investigated in murine models lacking Rac1 specifically in endothelium. Homozygous endothelial deletion was lethal, primarily due to defects in angiogenesis. Rac1-deficient endothelial cells were unable to form cellular protrusions/lamellipodia, leading to impaired cell-cell and cell-matrix interactions, and resulting in dysfunctional adhesion, motility, permeability and capillary morphogenesis. Development was normal in the heterozygous model, however a hypertensive phenotype was observed as a result of reduced nitric oxide signalling. Nitric oxide synthase activity was regulated by Rac1 at multiple levels; expression, mRNA stability and uptake of the nitric oxide synthase substrate L-arginine. Therefore, Rac1 activity is essential in regulating developmental and postnatal angiogenesis and cardiovascular function, by controlling nitric oxide production, and formation of endothelial cell protrusions.
authors.affiliation: Rayne Institute, Clinical Pharmacology, University College London, UK. L.Fiedler@ucl.ac.uk
authors.forename: Lorna R
authors.initials: LR
authors.lastname: Fiedler
mesh_terms: D000818:Animals; D002319:Cardiovascular System / Q000254:growth & development*; D004730:Endothelium, Vascular / Q000502:physiology*; D006801:Humans; D051379:Mice; D009479:Neuropeptides / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*; D020830:rac1 GTP-Binding Protein
chemical_list: D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein