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 (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 overl...

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Bibliographic Details
Published in:Journal of cardiovascular translational research 2022-02, Vol.15 (1), p.131-142
Main Authors: Li, Song-nan, Zhang, Jing-rui, Zhou, Lu, Xi, Hui, Li, Chang-yi, Zhao, Lei
Format: Article
Language:English
Subjects:
Aminobutyrates
Angiotensin II
Animals
Atrial Fibrillation - chemically induced
Atrial Fibrillation - prevention & control
Biomedical Engineering and Bioengineering
Biomedicine
Biphenyl Compounds
Cardiology
Fibrosis
Human Genetics
Medicine
Medicine & Public Health
Original Article
Rats
Signal Transduction
Valsartan - pharmacology
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Summary: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.
ISSN:1937-5387
1937-5395
DOI:10.1007/s12265-021-10137-5