Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Atherosclerosis / enzymology
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Atherosclerosis / etiology
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Atherosclerosis / physiopathology
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Atherosclerosis / prevention & control
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Cell Differentiation
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Cell Movement
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Cytoskeleton / metabolism
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Cytoskeleton / ultrastructure
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Endothelium, Vascular / enzymology
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Endothelium, Vascular / physiopathology
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Enzyme Activation
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Homeostasis
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Hypertension / enzymology
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Hypertension / physiopathology
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Models, Cardiovascular
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Muscle, Smooth, Vascular / enzymology
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Muscle, Smooth, Vascular / physiopathology
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Oxidative Stress
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Protein Prenylation / drug effects
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Protein Processing, Post-Translational / drug effects
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Signal Transduction
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Vascular Diseases / enzymology
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Vascular Diseases / physiopathology*
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rho GTP-Binding Proteins / antagonists & inhibitors
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rho GTP-Binding Proteins / classification
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rho GTP-Binding Proteins / genetics
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rho GTP-Binding Proteins / physiology*
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rhoA GTP-Binding Protein / physiology
Substances
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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rho GTP-Binding Proteins
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rhoA GTP-Binding Protein