1. Academic Validation
  2. Sacubitril/Valsartan Decreases Atrial Fibrillation Susceptibility by Inhibiting Angiotensin II-Induced Atrial Fibrosis Through p-Smad2/3, p-JNK, and p-p38 Signaling Pathways

Sacubitril/Valsartan Decreases Atrial Fibrillation Susceptibility by Inhibiting Angiotensin II-Induced Atrial Fibrosis Through p-Smad2/3, p-JNK, and p-p38 Signaling Pathways

  • J Cardiovasc Transl Res. 2022 Feb;15(1):131-142. doi: 10.1007/s12265-021-10137-5.
Song-Nan Li  # 1 Jing-Rui Zhang  # 1 Lu Zhou 1 Hui Xi 2 Chang-Yi Li 3 Lei Zhao 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chao Yang District, Beijing, 100029, China.
  • 2 Department of Cardiology, Peking University International Hospital, Beijing, China.
  • 3 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chao Yang District, Beijing, 100029, China. lichangyi1212@sina.com.
  • 4 Department of Radiololgy, Beijing Anzhen Hospital, Capital Medical University, Beijing, China. s2006430@126.com.
  • # Contributed equally.
Abstract

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.

Keywords

Angiotensin II; Atrial fibrillation; Atrial fibrosis; Sacubitril/valsartan.

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