Rho-kinase as a Novel Therapeutic Target in Treatment of Cardiovascular Diseases

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Abstract
Rho-kinase has been identified as one of the effectors of the small GTP-binding protein Rho. Accumulating evidence has demonstrated that the Rho/Rho-kinase-mediated pathway plays an important role in various cellular functions, not only in vascular smooth muscle contraction but also in actin cytoskeleton organization, cell adhesion and motility, cytokinesis, and gene expressions, all of which may be involved in the pathogenesis of arteriosclerosis/atherosclerosis. Indeed, animal experiments have demonstrated that Rho-kinase inhibitors effectively suppress coronary artery spasm and that long-term inhibition of Rho-kinase inhibits the development of coronary arteriosclerotic lesions and even causes regression of coronary vascular lesions in vivo. Recent clinical studies also have demonstrated the inhibitory effect of a Rho-kinase inhibitor on coronary artery spasm in patients with vasospastic angina and on exercise-induced myocardial ischemia in patients with stable effort angina with adequate safety. It is possible that Rho-kinase is also involved in the pathogenesis of other forms of cardiovascular diseases. Thus, Rho-kinase could be regarded as a novel therapeutic target in treatment of cardiovascular diseases.