Sodium Tanshinone IIA Sulfonate Prevents Angiotensin II-Induced Differentiation of Human Atrial Fibroblasts into Myofibroblasts.
Tangting ChenMiaoling LiXuehui FanJun ChengLiqun WangPublished in: Oxidative medicine and cellular longevity (2018)
Differentiation of atrial fibroblasts into myofibroblasts plays a critical role in atrial fibrosis. Sodium tanshinone IIA sulfonate (DS-201), a water-soluble derivative of tanshinone IIA, has been shown to have potent antifibrotic properties. However, the protective effects of DS-201 on angiotensin II- (Ang II-) induced differentiation of atrial fibroblasts into myofibroblasts remain to be elucidated. In this study, human atrial fibroblasts were stimulated with Ang II in the presence or absence of DS-201. Then, α-smooth muscle actin (α-SMA), collagen I, and collagen III expression and reactive oxygen species (ROS) generation were measured. The expression of transforming growth factor-β1 (TGF-β1) and the downstream signaling of TGF-β1, such as phosphorylation of Smad2/3, were also determined. The results demonstrated that DS-201 significantly prevented Ang II-induced human atrial fibroblast migration and decreased Ang II-induced α-SMA, collagen I, and collagen III expression. Furthermore, increased production of ROS and expression of TGF-β1 stimulated by Ang II were also significantly inhibited by DS-201. Consistent with these results, DS-201 significantly inhibited Ang II-evoked Smad2/3 phosphorylation and periostin expression. These results and the experiments involving N-acetyl cysteine (antioxidant) and an anti-TGF-β1 antibody suggest that DS-201 prevent Ang II-induced differentiation of atrial fibroblasts to myofibroblasts, at least in part, through suppressing oxidative stress and inhibiting the activation of TGF-β1 signaling pathway. All of these data indicate the potential utility of DS-201 for the treatment of cardiac fibrosis.
Keyphrases
- angiotensin ii
- transforming growth factor
- poor prognosis
- high glucose
- epithelial mesenchymal transition
- diabetic rats
- endothelial cells
- angiotensin converting enzyme
- atrial fibrillation
- vascular smooth muscle cells
- oxidative stress
- signaling pathway
- reactive oxygen species
- left atrial
- dna damage
- cell death
- smooth muscle
- extracellular matrix
- long non coding rna
- heart failure
- induced pluripotent stem cells
- left ventricular
- anti inflammatory
- mitral valve
- artificial intelligence
- tissue engineering
- smoking cessation
- single molecule
- combination therapy