Astragaloside IV alleviates heart failure by promoting angiogenesis through the JAK-STAT3 pathway.

CONTEXT: Heart failure (HF) is one of the most serious diseases worldwide. Astragaloside IV (ASI) is widely used for the treatment of cardiovascular disease in China.

OBJECTIVE

To evaluate the protective effect of ASI on the HF in a Sprague-Dawley rat model of left coronary artery ligation, and investigate the angiogenesis-related mechanisms.

MATERIALS AND

METHODS

Left coronary artery was ligated to induce a rat model of HF, and the rats were treated with vehicle (saline) or different doses of ASI (0.1, 0.3 and 1 mg/kg/day) by oral gavage for 6 weeks. Cardiac function was evaluated by echocardiography. Infarct size was determined by triphenyltetrazolium chloride staining. Cardiac vascular density was analyzed by microangiography. Real-time PCR, Western blot and chromatin immunoprecipitation were performed to investigate the mechanisms.

RESULTS

ASI treatment improved the body weight and survival rate of HF rats, as well as the cardiac function of HF rats, with significantly improved ejection fraction (75.27 ± 5.75% vs. 36.26 ± 4.14%) and fractional shortening (45.39 ± 3.66% vs. 17.88 ± 1.32%). ASI reduced the infarct size of the HF rats by 47%. ASI promoted angiogenesis, with increased vascular density (2.08-fold) and induced mRNA expression of CD31 (1.81-fold) and VEGF (2.70-fold) in the ischemic heart. Furthermore, ASI induced the phosphorylation of JAK (1.89-fold) and STAT3 (2.95-fold), as well as the activity of VEGF promoter which was regulated by STAT3.

DISCUSSION AND

CONCLUSIONS

ASI alleviated HF by promoting angiogenesis through JAK-STAT3 pathway, providing novel alternative strategies to prevent HF in the future.