1429-P: High Glucose-Stimulated Macrophage Exosomes Accelerate Atherosclerosis via miR-21-3p-Mediated VSMC Proliferation and Migration

Introduction and Objective: Atherosclerosis—the pathological foundation of most cardiovascular diseases. Macrophages can modulate gene expression in target cells through exosome-derived miRNA. Therefore, this study aims to investigate the molecular mechanisms by which diabetes accelerates atherosclerosis via macrophage-derived exosomes. Methods: Male ApoE-/- mice were fed a high-fat diet to establish a type 2 diabetes mellitus mouse model. Exosomes derived from control macrophages and macrophages stimulated with high glucose (HM-Exos) were extracted and purified using commercial isolation kits. The effects of HM-Exos on MOVAS cell proliferation and migration were assessed using scratch wound assays, Transwell migration assays, and EdU incorporation staining. Results: HM-Exos treatment increased the body weight of mice and aggravated the degree of atherosclerosis in their aorta. Co-culture of MOVAS cells with macrophages exposed to high-glucose conditions significantly enhanced MOVAS cell proliferation and migration, and these effects were clearly dependent on exosome-mediated signaling. Functional assays confirmed that miR-21-3p directly targets PTEN, thereby mediating the pro-proliferative and pro-migratory effects of HM-Exos on MOVAS cells. Conclusion: Type 2 diabetes promotes the secretion of macrophage-derived exosomes loaded with miR-21-3p and targets PTEN to enhance the proliferation and migration of MOVAS cells. Disclosure Y. Zhang: None. Q. Wan: None. Funding Ministry of Science and Technology of China and Science(2016YFC0901200); Technology Bureau of Luzhou City(2024JYJ038)