Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases
Rho-kinase as a novel therapeutic target in treatment of cardiovascular diseases
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DOI：
10.1097/00005344-200203000-00001
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发表时间：
2002-03-01
影响因子：
3
通讯作者：
Shimokawa, H
中科院分区：
文献类型：
--
作者：
Shimokawa, H
Rho 激酶已被确定为小 GTP 结合蛋白 Rho 的效应器之一。越来越多的证据表明，Rho/Rho激酶介导的通路在多种细胞功能中发挥着重要作用，不仅在血管平滑肌收缩中发挥着重要作用，而且在肌动蛋白细胞骨架组织、细胞粘附和运动、胞质分裂和基因表达等方面也发挥着重要作用，所有这些都可能参与动脉硬化/动脉粥样硬化的发病机制。事实上，动物实验已经证明Rho激酶抑制剂能有效抑制冠状动脉痉挛，长期抑制Rho激酶可以抑制冠状动脉硬化病变的发展，甚至使体内冠状血管病变消退。最近的临床研究还证明，Rho激酶抑制剂对血管痉挛性心绞痛患者的冠状动脉痉挛和稳定型劳累性心绞痛患者的运动诱发的心肌缺血有抑制作用，并且具有足够的安全性。 Rho 激酶也可能参与其他形式的心血管疾病的发病机制。因此，Rho激酶可被视为治疗心血管疾病的新靶点。
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.