Guo Qingbo, Huo Yiran, Liu Qiming, Zhou Shenghua, Xiao Yichao
Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China; Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China.
Department of Cardiovascular Medicine, Second Xiangya Hospital of Central South University, Changsha, Hunan, PR China.
Heart Rhythm. 2025 Jan;22(1):231-239. doi: 10.1016/j.hrthm.2024.07.118. Epub 2024 Aug 5.
Recent studies have highlighted the critical role of calcium/calmodulin-dependent protein kinase II (CaMKII) overactivation in the pathogenesis of various cardiac arrhythmias. Ruxolitinib, a Janus kinase inhibitor widely used for the treatment of myelofibrosis and acute graft-vs-host disease, has expanded its research horizons to include its potential as a CaMKII inhibitor in the treatment of cardiac arrhythmias. This article reviews the basic pharmacologic properties of ruxolitinib and delves into the role of CaMKII in cardiac arrhythmias, including its structural fundamentals, activation mechanisms, and association with arrhythmic conditions. Furthermore, the current state of CaMKII inhibitor research is discussed, with a special focus on the advances and clinical potential of ruxolitinib in this field. Studies indicate that ruxolitinib effectively inhibits CaMKII activity and has therapeutic potential against cardiac arrhythmias in animal models and at the cellular level. In addition, we address the critical issues that need to be resolved before the clinical application of ruxolitinib in arrhythmia treatment, including dosage concerns, long-term inhibitory effects, potential impacts on the nervous system, and efficacy across different types of arrhythmias. Future research directions involve further exploration of the clinical application potential of ruxolitinib, particularly in diseases such as heart failure, hypertrophic cardiomyopathy, dilated cardiomyopathy, and ischemic arrhythmias. In summary, the efficacy, low toxicity, and safety profile of ruxolitinib as a CaMKII inhibitor in the treatment of cardiac arrhythmias suggest a promising future for its development as a therapeutic drug in this domain.
近期研究突显了钙/钙调蛋白依赖性蛋白激酶II（CaMKII）过度激活在各种心律失常发病机制中的关键作用。芦可替尼是一种广泛用于治疗骨髓纤维化和急性移植物抗宿主病的Janus激酶抑制剂，其研究范围已扩展至包括作为CaMKII抑制剂在心律失常治疗中的潜力。本文综述了芦可替尼的基本药理特性，并深入探讨了CaMKII在心律失常中的作用，包括其结构基础、激活机制以及与心律失常状态的关联。此外，还讨论了CaMKII抑制剂的研究现状，特别关注芦可替尼在该领域的进展和临床潜力。研究表明，芦可替尼能有效抑制CaMKII活性，在动物模型和细胞水平上对心律失常具有治疗潜力。此外，我们还阐述了芦可替尼在心律失常治疗临床应用前需要解决的关键问题，包括剂量问题、长期抑制作用、对神经系统的潜在影响以及对不同类型心律失常的疗效。未来的研究方向包括进一步探索芦可替尼的临床应用潜力，特别是在心力衰竭、肥厚型心肌病、扩张型心肌病和缺血性心律失常等疾病中的应用。总之，芦可替尼作为CaMKII抑制剂在心律失常治疗中的疗效、低毒性和安全性表明其在该领域作为治疗药物具有广阔的发展前景。
