Department of Basic Medical Sciences, University of Arizona College of Medicine, Phoenix, AZ, USA.
Institute of Cardiovascular Sciences, St Boniface Hospital Albrechtsen Research Centre and Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Manitoba, Canada.
Cell Signal. 2021 Apr;80:109903. doi: 10.1016/j.cellsig.2020.109903. Epub 2020 Dec 25.
Angiotensin II (Ang II) is a primary mediator of profibrotic signaling in the heart and more specifically, the cardiac fibroblast. Ang II-mediated cardiomyocyte hypertrophy in combination with cardiac fibroblast proliferation, activation, and extracellular matrix production compromise cardiac function and increase mortality in humans. Profibrotic actions of Ang II are mediated by increasing production of fibrogenic mediators (e.g. transforming growth factor beta, scleraxis, osteopontin, and periostin), recruitment of immune cells, and via increased reactive oxygen species generation. Drugs that inhibit Ang II production or action, collectively referred to as renin angiotensin system (RAS) inhibitors, are first line therapeutics for heart failure. Moreover, transient RAS inhibition has been found to persistently alter hypertensive cardiac fibroblast responses to injury providing a useful tool to identify novel therapeutic targets. This review summarizes the profibrotic actions of Ang II and the known impact of RAS inhibition on cardiac fibroblast phenotype and cardiac remodeling.
血管紧张素 II（Ang II）是心脏中促纤维化信号的主要介质，更具体地说，是心脏成纤维细胞。Ang II 介导的心肌细胞肥大与心脏成纤维细胞增殖、激活和细胞外基质产生相结合，损害心脏功能并增加人类死亡率。Ang II 的促纤维化作用是通过增加纤维生成介质（例如转化生长因子β、肌腱蛋白 X、骨桥蛋白和骨膜蛋白）的产生、免疫细胞的募集以及增加活性氧的产生来介导的。抑制 Ang II 产生或作用的药物，统称为肾素-血管紧张素系统（RAS）抑制剂，是心力衰竭的一线治疗药物。此外，已经发现短暂的 RAS 抑制可持久改变高血压性心脏成纤维细胞对损伤的反应，为识别新的治疗靶点提供了有用的工具。本综述总结了 Ang II 的促纤维化作用以及 RAS 抑制对心脏成纤维细胞表型和心脏重塑的已知影响。
