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

Abstract

This systematic review examines the molecular mechanisms through which aerobicexercise influences cardiac apoptosis in patients with cardiovascular diseases (CVDs),which remain the leading cause of global mortality and are strongly linked to risk factorssuch as hypertension, diabetes, and sedentary lifestyles. Apoptosis, or programmed celldeath, plays a pivotal role in myocardial injury and disease progression in CVDs. Acomprehensive search of PubMed, Scopus, and Web of Science databases was conductedfor studies published between 2000 and 2025, yielding 60 initially relevant records. Afterapplying strict inclusion criteria (original research examining the effects of exercise oncardiac apoptosis) and exclusion criteria (methodological weaknesses, inadequate data, ora non-cardiac focus), eight studies were deemed eligible for detailed analysis. The findingsindicate 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), whilesimultaneously alleviating oxidative stress within cardiac tissue. In addition, regularaerobic training promotes mitochondrial homeostasis, enhances systemic circulation, andstrengthens overall cardiac performance, with particularly pronounced benefits in patientswith metabolic disorders. Nevertheless, the review highlights important limitations,most notably the small number of human clinical trials and the heterogeneity of exerciseprotocols across studies.