Molecular Mechanisms of Aerobic Exercise in Modulating Cardiac Apoptosis: A Systematic Review in Cardiovascular Patients

This systematic review examines the molecular mechanisms through which aerobic exercise influences cardiac apoptosis in patients with cardiovascular diseases (CVDs), which remain the leading cause of global mortality and are strongly linked to risk factors such as hypertension, diabetes, and sedentary lifestyles. Apoptosis, or programmed cell death, plays a pivotal role in myocardial injury and disease progression in CVDs. A comprehensive search of PubMed, Scopus, and Web of Science databases was conducted for studies published between 2000 and 2025, yielding 60 initially relevant records. After applying strict inclusion criteria (original research examining the effects of exercise on cardiac apoptosis) and exclusion criteria (methodological weaknesses, inadequate data, or a non-cardiac focus), eight studies were deemed eligible for detailed analysis. The findings indicate that aerobic exercise markedly reduces the expression of pro-apoptotic proteins, including caspase-3 (~47% reduction, p<0.01) and Bax (~43% reduction, p<0.01), while simultaneously alleviating oxidative stress within cardiac tissue. In addition, regular aerobic training promotes mitochondrial homeostasis, enhances systemic circulation, and strengthens overall cardiac performance, with particularly pronounced benefits in patients with metabolic disorders. Nevertheless, the review highlights important limitations, most notably the small number of human clinical trials and the heterogeneity of exercise protocols across studies.