A Review of Molecular Mechanisms, Inflammatory Factors, and Emerging Therapeutic Approaches in Atherosclerosis with an Emphasis on Physical Activity

Introduction: Cardiovascular diseases represent the leading cause of mortality worldwide, with atherosclerosis serving as the fundamental underlying pathology for the majority of these disorders. At present, atherosclerosis is recognized not merely as a lipid accumulation disorder, but as a complex inflammatory-immune process involving numerous molecular and cellular factors. This objective of this study aimed to comprehensively review the effects of physical activity and exercise training on atherosclerosis in terms of molecular mechanisms, inflammatory factors, and emerging therapeutic approaches, with a focus on exercise-based cardiac rehabilitation. Methods: This study was conducted as a narrative review. Sources were searched in reputable databases including PubMed, Web of Science, Scopus, Google Scholar, MagIran, SID, and Noormags using relevant keywords. The inclusion criteria were articles published in English between 2020 and 2025 and articles published in Persian between 1400 and 1405 (SH) on the effect of physical activity on atherosclerosis. Following screening and quality assessment based on the PRISMA guidelines, 15 key articles were ultimately included for final analysis. Results: The findings showed that exercise-based cardiac rehabilitation resulted in a 26% reduction in cardiovascular-related mortality alongside an 18% reduction in hospital readmissions. Exercise exerts its protective effects through reducing systemic inflammatory markers—with a 20–40% reduction in C-reactive protein (CRP)—improving endothelial function, increasing the production of anti-inflammatory myokines, and stabilizing atherosclerotic plaques. Conclusion: These results indicate that cardiac rehabilitation should be considered a standard component of treatment for patients with coronary artery disease. Future research should focus on determining the optimal exercise dose, identifying individual factors influencing the response to exercise, and developing rehabilitation programs based on digital technologies.