ST2 silencing aggravates ventricular remodeling and chronic heart failure in rats by mediating the IL-33/ST2 axis.

Heart failure appears to be a severe public health problem affecting millions of people worldwide. Knowledge of the molecular mechanism contributing to ventricular remodeling would allow for earlier prevention of heart failure. Evidence exists reporting the involvement of IL-33 and ST2 and in heart remodeling. Thus, this study aims to delineate the effects of ST2 on chronic heart failure (CHF) via the IL-33/ST2 axis. Coronary artery ligation was employed to simulate CHF in rats, which were characterized by transthoracic echocardiography for cardiac function. After that, ST2 silencing and IL-33 overexpression were induced in rat models to evaluate apoptosis and pathological alterations in myocardial tissues and serum levels of biochemical indices. It was revealed that cardiac function was impaired in response to ST2 silencing. Furthermore, ST2 knockdown suppressed the activities of the mitochondrial respiratory chain and accelerated cardiomyocyte apoptosis via blockade of the IL-33/ST2 axis. These findings suggest an inhibitory role of ST2 silencing on the IL-33/ST2 axis, which consequently increases the risk of cardiac dysfunction, accelerates ventricular remodeling, and aggravates heart failure in rats. This study highlights that ST2 silencing may be a novel potential preventive or therapeutic target for CHF.