The pathological cardiac functions of ankyrin repeat domain 1 (ANKRD1) in left ventricle can directly aggravate cardiac hypertrophy (CH) and fibrosis through the activation of extracellular signal-regulated kinase (ERK)/ transcription factor GATA binding protein 4 (GATA4) pathway, and subsequently contribute to heart failure (HF). Baoyuan Decoction (BYD), which is a famous classic Chinese medicinal formulation, has shown impressive cardioprotective effects clinically and experimentally. However, the knowledge is still limited in its underlying mechanisms against HF.
To explore whether BYD plays a protective role against HF by attenuating CH via the ANKRD1-ERK/GATA4 pathway.
In vivo, HF rat models were prepared using left anterior descending coronary artery (LADCA) ligation. Rats in the BYD group were administered a dosage of 2.57 g/kg of BYD for 28 days, while in the positive control group rats were given 4.67 mg/kg of Fosinopril. In vitro, a hypertrophic model was constructed by stimulating H9C2 cells with 1 uM Ang II. An ANKRD1-overexpressing cell model was established through transient transfection of ANKRD1 plasmid into H9C2 cells. Subsequently, BYD intervention was performed on the cell models to further elucidate its effects and underlying mechanism.
In vivo results showed that BYD significantly improved cardiac function and inhibited pathological hypertrophy and fibrosis in a rat model of HF post-acute myocardial infarction (AMI). Noticeably, label-free proteomic analysis demonstrated that BYD could reverse the CH-related biological turbulences, mainly through ANKRD1-ERK/GATA4 pathway. Further in vitro results validated that the hypertrophy was attenuated by BYD through suppression of AT1R, ANKRD1, Calpain1, p-ERK1/2 and p-GATA4. The results of in vitro model indicated that BYD could reverse the outcome of transfected over-expression of ANKRD1, including down-regulated expressions of ANKRD1, p-ERK1/2 and p-GATA4.
BYD ameliorates CH and improves HF through the ANKRD1-ERK/GATA4 pathway, providing a novel therapeutic option for the treatment of HF.

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