Rho and vascular disease.
The Rho family GTPases are regulatory molecules that link surface receptors to organisation of the actin cytoskeleton and play major roles in fundamental cellular processes. In the vasculature Rho signalling pathways are intimately involved in the regulation of endothelial barrier function, inflammation and transendothelial leukocyte migration, platelet activation, thrombosis and oxidative stress, as well as smooth muscle contraction, migration, proliferation and differentiation, and are thus implicated in many of the changes associated with atherogenesis. Indeed, it is believed that many of the beneficial, non-lipid lowering effects of statins occur as a result of their ability to inhibit Rho protein activation. Conversely, the Rho proteins can have beneficial effects on the vasculature, including the promotion of endothelial repair and the maintenance of SMC differentiation. Further identification of the mechanisms by which these proteins and their effectors act in the vasculature should lead to therapies that specifically target only the adverse effects of Rho signalling.
Centre for Research in Vascular Biology, School of Biomedical Sciences, University of Queensland, Qld 4072, Australia.
Barbara E
BE
Rolfe
Nathalie F
NF
Worth
Cameron J
CJ
World
Julie H
JH
Campbell
Gordon R
GR
Campbell
D050197:Atherosclerosis / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D002454:Cell Differentiation; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004730:Endothelium, Vascular / Q000201:enzymology / Q000503:physiopathology; D004789:Enzyme Activation; D006706:Homeostasis; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology / Q000503:physiopathology; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000503:physiopathology; D018384:Oxidative Stress; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction; D014652:Vascular Diseases / Q000201:enzymology / Q000503:physiopathology*; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein