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Rho Kinases and Cardiac Remodeling

机译:Rho激酶和心脏重塑

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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. ( Circ J 2016; 80: 1491–1498)
机译:高血压性心脏重塑的特征是左心室肥大和间质纤维化,可导致心力衰竭并保留射血分数。与Rho相关的卷曲螺旋激酶(ROCKs)是丝氨酸/苏氨酸蛋白激酶家族的成员,该家族介导小GTP结合蛋白RhoA的下游作用。有2种异构体:ROCK1和ROCK2。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(例如法舒地尔)的实验研究表明ROCK抑制在心脏重塑中的益处。在每种心脏重塑的病理模型中,缺少每种ROCK亚型的小鼠也表现出减少的心肌纤维化。确实,法舒地尔的临床研究表明,ROCKs可能是心血管疾病的潜在新型治疗靶标。在这篇综述中,我们总结了目前对ROCKs在心脏纤维化和肥大中的作用的理解,并讨论了ROCKs对有害心脏重构的治疗潜力。 (Circ J 2016; 80:1491–1498)

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