Astragaloside IV alleviates heart failure by regulating SUMO‑specific protease 1
Juan Liu, Ya Li, Xiyun Bian, Na Xue, Jiancai Yu, Shipeng Dai, Xiaozhi Liu
Abstract
The present study investigated whether the protective effect and mechanism of astragaloside IV (AS‑IV) on heart failure (HF) involves small ubiquitin‑like modifier (SUMO)‑specific protease 1 (Senp1). Mouse HF was established by aortic constriction, inducing pressure overload. The model was confirmed by echocardiography 6 weeks after surgery. Mice were randomly divided into control, HF, HF+AS‑IV, and AS‑IV groups. Ventricular function was examined by echocardiography. Morphological changes of myocardial tissues were examined by H&E staining. The protein levels of the apoptosis‑related proteins, cleaved caspase‑3, caspase‑3, Bcl2, Bax, and SUMO‑Senp1 were determined by Western blotting. H<sub>2</sub>O<sub>2</sub> in isolated mitochondria and cells was determined by Amplex Red. A reactive oxygen species (ROS) detection kit determined ROS levels in isolated mitochondria and HL‑1 cells. JC‑1 reagent measured mitochondrial membrane potential (ΔΨm). Apoptosis of HL‑1 cells was examined by terminal deoxynucleotidyl transferase dUTP nick end labeling. Compared with the control group, the heart weight and heart mass/body weight ratio increased in the HF group (P<0.05). Furthermore, the ejection fraction and left ventricular shortening fraction decreased (P<0.05), while the left ventricular end‑diastolic diameter (LVID;d) and end‑systolic diameter (LVID;s) increased (P<0.05). Finally, mitochondrial ROS and H<sub>2</sub>O<sub>2</sub> increased (P<0.05), while the ΔΨm decreased (P<0.05). However, AS‑IV improved the cardiac function of HF mice, decreased the level of ROS and H<sub>2</sub>O<sub>2</sub> in the myocardium, suppressed the decrease in ΔΨm, and decreased the apoptosis of myocardial cells (P<0.05). AS‑IV also decreased the Senp1‑overexpression. Furthermore, in HL‑1 cells, Senp1‑overexpression significantly inhibited the protective effects of AS‑IV. AS‑IV decreased oxidative stress in cardiomyocytes, decreased mitochondrial damage, inhibited ventricular remodeling, and ultimately improved cardiac function by inhibiting HF‑induced Senp1‑overexpression. This mechanism provides a novel theoretical basis and clinical treatment for HF.