Guanxin V protects against ventricular remodeling after acute myocardial infarction through the interaction of TGF-β1 and Vimentin

Abstract

Background: Our previous study demonstrated that Guanxin V (GXV), a traditional Chinese herbal medicine, has a significant therapeutic effect on ventricular remodeling. However, the mechanistic action of GXV in ventricular remodeling warrants clarification.

Purpose: Here, we aimed to explore the anti-ventricular remodeling contribution of GXV and to provide an experimental basis for clinical generalization.

Methods: A ventricular remodeling model after acute myocardial infarction was constructed in Syrian hamsters. The echocardiography and biochemical indices of cardiac function and remodeling were evaluated in different groups. Moreover, we built a remodeling model in cardiomyocytes and further explored the mechanism. Transmission electron microscopy was used to observe the ultrastructure of cardiomyocytes. The vital markers involved in the signaling pathway were detected by RT-qPCR and immunoblotting. Transforming growth factor beta 1 (TGF-β1) was overexpressed with lentivirus to verify the necessity of TGF-β1 in GXV's anti-ventricular remodeling effect. Finally, co-immunoprecipitation was conducted to test the interaction of TGF-β1 and Vimentin.

Results: In hamster cardiac remodeling induced by acute myocardial infarction, GXV alleviated apoptosis, cardiac hypertrophy, and cardiac remodeling, and even improved cardiac function. Mechanistically, GXV inhibited the remodeling process by directly targeting TGF-β1. Overexpression of TGF-β1 exacerbated the ventricular remodeling, whereas GXV reversed this dysregulation. GXV also decreased the up-regulated Vimentin level in pathological ventricular remodeling. Moreover, the interaction of Vimentin and TGF-β1 was confirmed by co-immunoprecipitation, and GXV impeded this interaction.

Conclusion: We showed that the interaction of Vimentin and TGF-β1 may be a novel target for ventricular remodeling and that GXV might be a new agent to fight against ventricular remodeling by targeting TGF-β1 and impeding its interaction with Vimentin.

Keywords: Acute myocardial infarction; Guanxin V; TGF-β1; Traditional Chinese medicine; Ventricular remodeling; Vimentin.