Astragaloside IV inhibits angiotensin II-induced atrial fibrosis and atrial fibrillation by SIRT1/PGC-1α/FNDC5 pathway
- Heliyon. 2024 May 9;10(10):e30984. doi: 10.1016/j.heliyon.2024.e30984.
- 1. Department of Cardiology, Shanghai Pudong New Area Zhoupu Hospital (Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital), No.1500 Zhou Yuan Road, Pudong New District, Shanghai, 201318, China.
Aims and objectives: Astragaloside IV (AS-IV) has been found to possess anti-oxidative, anti-inflammatory, and anti-apoptotic properties, but its effect on atrial fibrosis is yet to be determined. This research investigates the protective role of AS-IV in angiotensin II (Ang II)-induced atrial fibrosis and atrial fibrillation (AF).
Methods: C57BL/6 male mice aged 8-10 weeks (n = 40) were subcutaneously administered Ang II (2.0 mg/kg/day) or saline, with AS-IV (80 mg/kg) intraperitoneally administered 2 h before Ang II infusion for 4 weeks. Biochemical, histological, and morphological analyses were carried out. Using transesophageal burst pacing, AF was generated in vivo.
Results: Here, we report that AS-IV treatment inhibited Ang II-induced AF development in mice (58 ± 5.86 vs 15.13 ± 2.16 %, p < 0.001). Ang II + AS-IV therapy was effective in reducing the atrial fibrotic area and decreasing the increase in smooth muscle alpha-actin (α-SMA)-positive myofibroblasts brought on by Ang II treatment (fibrotic area: 26.25 ± 3.81 vs 8.62 ± 1.83 %, p < 0.001 and α-SMA: 65.62 ± 10.63 vs 17.25 ± 1.78 %, p < 0.001). The Reactive Oxygen Species (ROS) production was reduced by pretreatment with Ang II + AS-IV (9.20 ± 0.92 vs 2.63 ± 0.22 %/sec, p < 0.001). In addition, Ang II + AS-IV treatment suppressed oxidative stress in Ang II-induced atrial fibrosis (malondialdehyde: 701.78 ± 85.01 vs 504.07 ± 25.62 pmol/mg protein, p < 0.001; superoxide dismutase: 13.82 ± 1.25 vs 29.54 ± 2.45 U/mg protein, p < 0.001 and catalase: 11.43 ± 1.19 vs 20.83 ± 3.29 U/mg protein, p < 0.001, respectively). Moreover, Ang II + AS-IV decreased the expression of α-SMA, Collagen III and Collagen I (3.32 ± 0.53 vs 1.41 ± 0.20 fold, p < 0.001; 3.41 ± 0.55 vs 1.48 ± 0.18 fold, p < 0.001; 2.34 ± 0.55 vs 0.99 ± 0.17 fold, p < 0.001, respectively) while increasing the protein expression of Sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), and fibronectin type III domain-containing protein 5 (FNDC5) in Ang II-treated mice (0.22 ± 0.02 vs 0.57 ± 0.08 fold, p < 0.001; 0.28 ± 0.04 vs 0.72 ± 0.05 fold, p < 0.001; 0.38 ± 0.03 vs 0.68 ± 0.06 fold, p < 0.001, respectively).
Conclusion: Our data led us to speculate that AS-IV may protect against Ang II-induced atrial fibrosis and AF via upregulation of the SIRT1/PGC-1α/FNDC5 pathway.