Aerobic Exercise Modalities and the Mitigation of Atherosclerotic Pathways: A Systematic Review of Molecular Signaling.

Background: Cardiovascular disease secondary to arterial plaque formation remains a major global health burden. Clinical practice widely recognizes the benefits of physical conditioning, yet the exact vascular-level pathways through which aerobic work interrupts plaque progression warrant closer synthesis. This paper reviews the underlying molecular networks influenced by regular endurance training. Methods: Utilizing the PRISMA framework, a systematic extraction of data from PubMed and Scopus was conducted. The focus centered on papers detailing endothelial responses, macrophage modulation, and structural remodeling under aerobic physical stress over the past ten years. Results: The cardioprotective profile of aerobic training stems from distinct cellular events. Rhythmic fluid movement elevates sustained laminar shear forces, activating the KLF2/NRF2 axis and securing eNOS integrity. At the immune level, physical stress upregulates Sestrin 1 (SESN1), effectively blunting NLRP3 inflammasome processing and lowering IL-1β expression. Furthermore, tissue clearance of lipids improves through enhanced ABCA1 pathways, while the down-regulation of matrix metalloproteinases (MMP-9 and MMP-13) prevents fibrous cap degradation. Conclusion: Enductive physical training serves as a multi-target physiological intervention that stabilizes the endothelial phenotype and delays lipid core expansion. Understanding these specific mechanisms helps refine exercise prescriptions in clinical sports cardiology. Keywords: Vascular Shearing, Sestrin 1, Inflammasome Inhibition, Plaque Integrity, Myokines.