Salvianolic Acid B Alleviates Atrial Fibrillation-Associated Fibrosis With Modulation of COL1A2 and the PI3K-AKT Pathway.
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.
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.
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.
Sal-B alleviates AF in association with COL1A2 modulation and PI3K-AKT signaling pathway inhibition, which may contribute to reducing atrial fibrosis.
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.
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.
Sal-B alleviates AF in association with COL1A2 modulation and PI3K-AKT signaling pathway inhibition, which may contribute to reducing atrial fibrosis.