Astragaloside IV inhibits angiotensin II-induced atrial fibrosis and atrial fibrillation by SIRT1/PGC-1α/FNDC5 pathway.
Heliyon
; 10(10): e30984, 2024 May 30.
Article
em En
| MEDLINE
| ID: mdl-38803993
ABSTRACT
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.
Texto completo:
1
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article