Background <p>Atherosclerosis (AS) is a primary driver of cardiovascular diseases, with vascular smooth muscle cell (VSMC) fate being critical for plaque stability. Macrophage extracellular traps (METs) are implicated in AS, but their precise impact on VSMCs remains unclear. This study investigated the role of METs in VSMC necroptosis, phenotypic switching, and AS progression.</p> Method <p>An ApoE^−/− mouse model was utilized, with intraperitoneal injection of exogenous METs. Atherosclerotic plaque burden was assessed via Oil Red O, H&amp;E, and Masson staining. MPO-DNA complexes, inflammatory cytokines, and necrotic markers were quantified by ELISA. In vitro, VSMCs were treated with ox-LDL, METs, and pathway inhibitors to evaluate necroptosis, contractile/synthetic phenotype markers, and Rap1 signaling pathway activation.</p> Results <p>Exogenous METs administration exacerbated AS plaque burden in ApoE^−/− mice, characterized by increased plaque area, reduced collagen content, and thinner fibrous caps. METs also amplified systemic inflammation, dyslipidemia, and necroptosis-driven plaque destabilization. Bioinformatic analysis revealed a strong association between METs and necroptosis in unstable plaques. In vitro, METs triggered VSMC necroptosis and upregulated synthetic phenotype markers. Mechanistically, the Rap1-MEK5-ERK5/p38 signaling axis was activated in METs-treated VSMCs and AS plaques. Pharmacological inhibition of Rap1 signaling attenuated plaque progression and suppressed VSMC necroptosis and phenotypic switching. Additionally, METs were internalized by VSMCs via endocytosis.</p> Conclusion <p>Our findings demonstrate that METs are endocytosed by VSMCs, activating the Rap1-MEK5-ERK5/p38 cascade to drive necroptosis and synthetic phenotypic transition, thereby accelerating AS progression. These insights provide a molecular foundation for developing novel therapies targeting METs or the Rap1 pathway to stabilize vulnerable plaques.</p>