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Salvianolic Acid B Alleviates Atrial Fibrillation-Associated Fibrosis With Modulation of COL1A2 and the PI3K-AKT
Pengran Wang1,2, Jianhua Ma3, Jianlong Li2
1Department of Cardiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China, hebmu.edu.cn.
Background:
Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, is strongly associated with atrial fibrosis. Salvianolic acid B (Sal-B), a bioactive compound extracted from Salvia miltiorrhiza, demonstrates cardioprotective properties, though its specific role in AF remains to be elucidated.
Methods:
Transcriptome analysis of the GSE115574 dataset was performed to identify COL1A2 as a differentially expressed gene in patients with AF. Molecular docking simulations were performed to evaluate the binding affinity between Sal-B and COL1A2. For in vitro experiments, an injury model was established in AC16 cardiomyocytes using Angiotensin II (Ang-II) treatment, followed by intervention with either Sal-B (80 μg/mL) or COL1A2 siRNA. Cellular viability, apoptosis, migration capacity, and fibrosis markers (COL1A1, α-SMA, and collagen III) were subsequently assessed. In vivo studies employed an ACh-CaCl2-induced AF rat model, with cardiac function evaluated through electrocardiography (ECG) and echocardiography. Myocardial tissue damage was examined via hematoxylin-eosin (HE) staining and Masson's trichrome staining. Western blot analysis was used to determine COL1A2 expression and PI3K-AKT pathway activity.
Results:
COL1A2 expression was significantly upregulated in AF, and molecular docking demonstrated its strong binding affinity for Sal-B. Sal-B treatment rescued Ang-II-induced cardiomyocyte damage, reduced apoptosis, and suppressed fibrosis marker expression. In rat models, either Sal-B or si-COL1A2 alone shortened the AF duration, improved cardiac function (attenuated the elevated E/E' ratio while restoring the ejection fraction), and reduced fibrosis and inflammation. The combined treatment synergistically restored sinus rhythm and normalized collagen deposition, suggesting a modulatory role of Sal-B in these processes.
Conclusions:
Sal-B alleviates AF in association with COL1A2 modulation and PI3K-AKT signaling pathway inhibition, which may contribute to reducing atrial fibrosis.
