Rho Kinases and Cardiac Remodeling.
Rho Kinases and Cardiac Remodeling.
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DOI：
10.1253/circj.cj-16-0433
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发表时间：
2016-06-24
期刊：
影响因子：
--
通讯作者：
Liao JK
中科院分区：
文献类型：
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作者：
Shimizu T;Liao JK
高血压性心脏重构以左心室肥厚和间质纤维化为特征，可导致射血分数保留的心力衰竭。Rho相关卷曲螺旋激酶（ROCK）是丝氨酸/苏氨酸蛋白激酶家族的成员，其介导小GTP结合蛋白RhoA的下游效应。有两种亚型：ROCK 1和ROCK 2。它们在不同类型的细胞和组织中具有不同的功能。越来越多的证据表明，ROCK有助于心血管疾病的发展，包括心脏纤维化、肥大和随后的心力衰竭。最近使用ROCK抑制剂（如法舒地尔）的实验研究显示了ROCK抑制在心脏重塑中的益处。缺乏每种ROCK同种型的小鼠在各种心脏重塑的病理模型中也表现出减少的心肌纤维化。事实上，法舒地尔的临床研究表明，ROCK可能是心血管疾病的潜在新治疗靶点。在这篇综述中，我们总结了目前对ROCKs在心脏纤维化和肥大发展中的作用的认识，并讨论了其对有害心脏重塑的治疗潜力。
Hypertensive cardiac remodeling is characterized by left ventricular hypertrophy and interstitial fibrosis, which can lead to heart failure with preserved ejection fraction. The Rho-associated coiled-coil containing kinases (ROCKs) are members of the serine/threonine protein kinase family, which mediates the downstream effects of the small GTP-binding protein RhoA. There are 2 isoforms: ROCK1 and ROCK2. They have different functions in different types of cells and tissues. There is growing evidence that ROCKs contribute to the development of cardiovascular diseases, including cardiac fibrosis, hypertrophy, and subsequent heart failure. Recent experimental studies using ROCK inhibitors, such as fasudil, have shown the benefits of ROCK inhibition in cardiac remodeling. Mice lacking each ROCK isoform also exhibit reduced myocardial fibrosis in a variety of pathological models of cardiac remodeling. Indeed, clinical studies with fasudil have suggested that ROCKs could be potential novel therapeutic targets for cardiovascular diseases. In this review, we summarize the current understanding of the roles of ROCKs in the development of cardiac fibrosis and hypertrophy and discuss their therapeutic potential for deleterious cardiac remodeling.