The Underlying Mechanism Of Qiliqiangxin Extract Inhibits Angiotensin Ⅱ-induced Cardiac Fibroblasts Transdifferentiation Through Blocking Smad3 Pathway

Backgrounds: Qiliqiangxin extract(QL), a traditional Chinese medicine, had long been used to treat chronic heart failure. It’s consisting of Radix astragali, Ginseng, Aconite Root, Salvia miltiorrhiza and so on. Recent studies revealed that differentiation of cardiac fibroblasts(CFs) into myofibroblasts played an important role in cardiac remodeling and development of heart failure, however little was known about whether QL ameliorated myocardial remodeling via regulating CFs differentiation. The present study aimed to investigate the effects of QL on angiotensin II(Ang II)-induced CFs transdifferentiation and the underlying mechanism.Objective: To investigate the role of Qiliqiangxin extract in cardiac fibroblasts transdifferentiation induced by angiotensin II and the underlying mechanism.Methods: Primary cultures of cardiac fibroblasts were isolated from neonatal SD rats and digested by trypsin. Cells were randomly divided into 4 groups: control group, Ang II treated group(10-6mol/l), Qiliqiangxin extract treated group(0.5mg/ml), and Ang II with Qiliqiangxin extract treated group. CFs were pretreated with Qiliqiangxin for 1h followed by angiotensin II processing for 6h. Nucleus and cytoplasm protein were extracted. The protein expressions of α-SMA, TGF-βl and its downstream Smad3, phosphorylated Smad3, Smad6 were detected with Western blotting or immunocytofluorescence.Results: Angiotensin II enhanced α-SMA and TGF-βl in cardiac fibroblasts, which was significantly downregulated by Qiliqiangxin. Meanwhile, Qiliqiangxin also decreased the phosphorylation level of Smad3, and increased expressions of Smad6.Conclusion: Qiliqiangxin extract inhibits Angiotensin II-induced cardiac fibroblasts transdifferentiation through TGF-βl-mediated Smad3 pathway, which may be involved in its cardiac reverse remodeling and heart failure improvement.