Sacubitril/valsartan (SAC/VAL) prevents angiotensin II (AngII) from binding AT1-R and blocks degradation of natriuretic peptides. Despite its efficacy in reducing ventricular fibrosis and preserving cardiac functions, which has been extensively demonstrated in myocardial infarction or pressure overload models, few studies have been conducted to determine whether SAC/VAL could attenuate atrial fibrosis and decrease atrial fibrillation (AF) susceptibility. Our study provided evidence for the inhibition of atrial fibrosis and reduced susceptibility to AF by SAC/VAL. After 28 days of AngII continuous subcutaneous stimulation, rats in SAC/VAL group exhibited reduced extent of atrial fibrosis, inhibited proliferation, migration, and differentiation of atrial fibroblasts, and decreased susceptibility to AF. We further found that inhibition of p-Smad2/3, p-JNK, and p-p38MAPK pathways is involved in the role of SAC/VAL on AngII-induced atrial fibrosis in vivo. These results emphasize the importance of SAC/VAL in the prevention of AngII-induced atrial fibrosis and may help to enrich the options for AF pharmacotherapy.

Sacubitril/valsartan (SAC/VAL) 防止血管紧张素 II (AngII) 结合 AT1-R 并阻止利钠肽的降解。尽管其在减少心室纤维化和保护心脏功能方面的功效已在心肌梗死或压力过载模型中得到广泛证明，但很少有研究确定 SAC/VAL 是否可以减轻心房纤维化和降低心房颤动 (AF) 易感性。我们的研究为 SAC/VAL 抑制心房纤维化和降低对 AF 的易感性提供了证据。AngII连续皮下刺激28天后，SAC/VAL组大鼠心房纤维化程度降低，心房成纤维细胞增殖、迁移和分化受到抑制，AF易感性降低。我们进一步发现抑制 p-Smad2/3，p-JNK 和 p-p38MAPK 通路参与 SAC/VAL 在 AngII 诱导的体内心房纤维化中的作用。这些结果强调了 SAC/VAL 在预防 AngII 诱导的心房纤维化中的重要性，并可能有助于丰富 AF 药物治疗的选择。