Adropin Improves Radiation-Induced Myocardial Injury via VEGFR2/PI3K/Akt Pathway

Abstract

Mediastinal cancer radiotherapy exposes the heart and causes myocardial injury. It is of utmost importance to identify effective prevention and treatment targets. In this study, the regulatory role of adropin (Ad) in radiation-induced myocardial injury (RIMI) was explored in mice. After C57BL/6 mice were administered E0771 cells and received radiotherapy, the effects of exogenous Ad intervention on myocardial fibrosis, apoptosis, microvessel density, oxidative stress, and protein expression levels were observed. The results showed that exogenous Ad effectively improved cardiac function, suppressed oxidative stress, inhibited myocardial fibrosis, reduced myocardial apoptosis, and promoted microangiogenesis in RIMI mice. Ad also downregulated the expression levels of transforming growth factor β1 (TGF-β1), NADPH oxidase 4 (NOX4), and cleaved caspase 3 and upregulated the expression of phosphor-endothelial nitric oxide synthase (p-eNOS). However, the above-mentioned effects of Ad were significantly reversed in Ad-/- mice. Radiotherapy resulted in the downregulation of phosphor-vascular endothelial growth factor receptor (p-VEGFR2) and p-Akt in myocardial tissue, which were upregulated by Ad. However, after targeted inhibition of VEGFR2 with apatinib, the effect of Ad on improving RIMI was significantly reversed. Taken together, exogenous Ad significantly ameliorated RIMI by reducing oxidative stress, promoting microangiogenesis, and inhibiting myocardial fibrosis and apoptosis. The underlying molecular mechanism involved may be elucidated by activation of the VEGFR2/PI3K/Akt pathway.