Astragaloside IV prevents myocardial hypertrophy induced by mechanical stress by activating autophagy and reducing inflammation

The aim of the present study was to investigate the effects of astragaloside IV (As-IV) on mechanical stress-induced myocardial hypertrophy, with a focus on autophagy and inflammation.

As-IV prevents myocardial hypertrophy induced by mechanical stress by activating autophagy and reducing inflammation.

A rat cardiac hypertrophy model was established by narrowing the abdominal aorta, and a cell hypertrophy model was established by mechanically stretching primary cardiomyocytes. Cardiac function index and cardiac hypertrophy were measured by echocardiography, heart weight index (HWI) and left ventriculus weight index (LVWI) in vivo. Cell size was measured by phalloidin-tetramethyl treatment in vitro, while hematoxylin and eosin (HE) staining was used to observe the arrangement and morphology of myocardial cells. The expression of ANP, BNP, LC3II, p62, NLRP3, and IL-1β in both myocardial tissue and cardiomyocytes was assessed by Western blot, while TNF-α and IL-18 levels in serum and cell supernatants were measured by ELISA.

In the aortic banding model, the cardiac function index LVEF was decreased; the hypertrophy indexes LVPWd, LVPWs, IVSd and IVSs were significantly increased; cardiomyocytes were enlarged and disordered; the expression levels of ANP, BNP, NLRP3, IL-1β and p62 were increased; and LC3II expression was decreased in both myocardial tissue and cardiomyocytes. As-IV could significantly improve cardiac function and cardiomyocyte morphology and limit hypertrophy, thereby protecting damaged hearts, while rapamycin had a similar effect as As-IV. In addition, As-IV decreased the expression of NLRP3 and IL-1β and activated autophagy, as evidenced by increased LC3II expression and decreased p62 levels.