Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom.
Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy.
Curr Cardiol Rev. 2023;19(3):e171122210986. doi: 10.2174/1573403X19666221117092951.
Among the complex mechanisms of AF pathogenesis, intracellular calcium overload and oxidative stress play a major role, both triggered by inflammatory processes. The additional basic event taking place in AF is atrial fibrotic remodeling, again triggered by oxidative stress, which is determined by connexins rearrangement and differentiation of fibroblasts into active collagensecreting myofibroblasts. RhoA/ROCK system is the final pathway of a wide spectrum of molecular effectors such as Angiotensin II, platelet-derived growth factor, connective tissue growth factor and transforming growth factor β, that overall determine calcium dysregulation and pro-fibrotic remodeling. Both in experimental and clinical studies, RhoA/ROCK activation has been linked to superoxide ion production, fibrotic remodeling and connexins rearrangement, with important consequences for AF pathogenesis. ROCK pathway inhibition may therefore be a therapeutic or preventive target for special AF subgroups of patients.
在房颤发病机制的复杂机制中，细胞内钙超载和氧化应激起着重要作用，两者均由炎症过程引发。房颤中发生的另一个基本事件是心房纤维化重塑，同样由氧化应激触发，这是由连接蛋白重排和成纤维细胞分化为活跃的胶原分泌肌成纤维细胞决定的。RhoA/ROCK 系统是广泛的分子效应物（如血管紧张素 II、血小板衍生生长因子、结缔组织生长因子和转化生长因子 β）的最终途径，这些分子效应物总体上决定了钙失调和促纤维化重塑。在实验和临床研究中，RhoA/ROCK 的激活与超氧阴离子的产生、纤维化重塑和连接蛋白重排有关，对房颤的发病机制有重要影响。因此，ROCK 通路抑制可能是房颤特殊亚组患者的一种治疗或预防靶点。
