Department of Experimental Medicine, Section of Pharmacology L. Donatelli, University of Campania "Luigi Vanvitelli", Via Santa Maria di Costantinopoli 16, 80138, Naples, Italy.
IRCCS San Raffaele Pisana, Rome, Italy.
Heart Fail Rev. 2020 Mar;25(2):367-380. doi: 10.1007/s10741-019-09837-7.
Atrial fibrillation (AF) is a significant cause of morbidity and mortality as well as a public health burden considering the high costs of AF-related hospitalizations. Pre-clinical and clinical evidence showed a potential role of the renin angiotensin system (RAS) in the etiopathogenesis of AF. Among RAS mediators, angiotensin II (AII) and angiotensin 1-7 (A1-7) have been mostly investigated in AF. Specifically, the stimulation of the pathway mediated by AII or the inhibition of the pathway mediated by A1-7 may participate in inducing and sustaining AF. In this review, we summarize the evidence showing that both RAS pathways may balance the onset of AF through different biological mechanisms involving inflammation, epicardial adipose tissue (EAT) accumulation, and electrical cardiac remodeling. EAT is a predictor for AF as it may induce its onset through direct (infiltration of epicardial adipocytes into the underlying atrial myocardium) and indirect (release of inflammatory adipokines, the stimulation of oxidative stress, macrophage phenotype switching, and AF triggers) mechanisms. Classic RAS blockers such as angiotensin converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARB) may prevent AF by affecting the accumulation of the EAT, representing a useful therapeutic strategy for preventing AF especially in patients with heart failure and known left ventricular dysfunction. Further studies are necessary to prove this benefit in patients with other cardiovascular diseases. Finally, the possibility of using the A1-7 or ACE2 analogues, to enlarge current therapeutic options for AF, may represent an important field of research.
心房颤动（AF）是发病率和死亡率的重要原因，也是公共卫生负担，因为与 AF 相关的住院治疗费用高昂。临床前和临床证据表明肾素-血管紧张素系统（RAS）在 AF 的发病机制中具有潜在作用。在 RAS 介质中，血管紧张素 II（AII）和血管紧张素 1-7（A1-7）在 AF 中得到了最多的研究。具体来说，AII 介导的途径的刺激或 A1-7 介导的途径的抑制可能参与诱导和维持 AF。在这篇综述中，我们总结了证据表明，RAS 两条途径都可能通过涉及炎症、心外膜脂肪组织（EAT）积聚和电心脏重构的不同生物学机制来平衡 AF 的发生。EAT 是 AF 的预测因子，因为它可能通过直接（心外膜脂肪细胞浸润到下伏的心房心肌）和间接（炎症脂肪因子的释放、氧化应激的刺激、巨噬细胞表型转换和 AF 触发）机制引发 AF。经典的 RAS 阻滞剂，如血管紧张素转换酶抑制剂（ACE-I）和血管紧张素受体阻滞剂（ARB），可能通过影响 EAT 的积聚来预防 AF，这代表了预防 AF 的一种有用的治疗策略，特别是在心力衰竭和已知左心室功能障碍的患者中。需要进一步的研究来证明这对其他心血管疾病患者的益处。最后，使用 A1-7 或 ACE2 类似物来扩大 AF 的当前治疗选择的可能性，可能代表一个重要的研究领域。
