Different Intensities of Exercise Affect the Prognosis of Ventricular Aneurysm in Mice by Regulating the Progression of Cardiac Fibrosis.

Ventricular aneurysm is a serious complication following myocardial infarction. Increasing evidence suggests that exercise-based cardiac rehabilitation plays a protective role in cardiovascular disease. However, the effects of exercise on ventricular aneurysm and the underlying mechanisms remain poorly understood. Therefore, this study aimed to establish a murine model of ventricular aneurysm and investigate the impact of exercise on this condition, along with its potential mechanisms. In this study, using proximal coronary artery ligation, a murine cardiac ventricular aneurysm model was established and evaluated by real-time myocardial contrast echocardiography. Wild-type male C57BL/6 mice with ventricular aneurysms were randomly assigned to three groups: a Sedentary group (no exercise, n = 7), a moderate-intensity exercise group (5 m/min adaptive exercise for 2 weeks, followed by 12-m/min moderate-intensity exercise for 8 weeks, n = 9), and a high-intensity exercise group (5-m/min adaptive exercise for 2 weeks, followed by 18-m/min high-intensity exercise for 8 weeks, n = 7). After 8 weeks of exercise intervention, moderate-intensity exercise was found to significantly enhance cardiac function, reduce myocardial fibrosis, and inhibit fibroblast activation. In contrast, high-intensity exercise resulted in deteriorated cardiac function and aggravated cardiac injury. Mechanistically, this paradoxical effect was linked to the regulation of PTEN stability and subsequent modulation of Smad2/3 signaling pathway. This study provides a theoretical foundation for the role of exercise in managing ventricular aneurysms and offers insights into optimal exercise intensity levels.