Recent evidence for an involvement of rho-kinase in cerebral vascular disease.
OBJECTIVE
The small G protein rhoA and its downstream effector rho-kinase are both expressed in vascular cells and are involved in several cellular processes. One of these processes is the regulation of the phosphorylation state of myosin light chain in vascular muscle and thus, the development of force. Recently, considerable evidence for increased activity of this pathway in cerebral and noncerebral vessels has been reported in several cardiovascular diseases associated with increased vascular tone.


RESULTS
The main aim of this brief review is to summarize current evidence for the involvement of rhoA/rho-kinase signaling in dysfunction of the cerebral circulation in disease states, such as cerebral vasospasm, hypertension, diabetes, and ischemic brain injury. We will also briefly consider the novel hypothesis that augmented activity of endothelial rho-kinase decreases nitric oxide production and contributes to increased vascular tone in disease and the possibility of this action being a key therapeutic target of statins (inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase) in cerebral and noncerebral arteries.


CONCLUSIONS
Considerable evidence indicates that rhoA/rho-kinase activity is commonly increased in cerebral vascular disease, not only in vascular muscle, but also in the endothelium and possibly in inflammatory cells and neurons.
Chrissobolis
Sophocles
S
Department of Internal Medicine, University of Iowa, Iowa City, USA.
Sobey
Christopher G
CG
D001808:Blood Vessels / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D002561:Cerebrovascular Disorders / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein