FoxO3a regulated by miR-150-5p promotes the pyroptosis of macrophages in atherosclerosis.

BACKGROUND: This study uses tissue exosome analysis to explore the role of miR-150-5p and its downstream genes in atherosclerosis (AS), an area where the functional mechanisms and pathophysiological significance of exosomal miR-150-5p remain poorly understood. METHODS: Exosomes from AS mouse vascular tissue were analyzed to identify miR-150-5p target genes. Dual luciferase assays validated miRNA-target interactions, while RT-qPCR and Western blot assessed FoxO3a expression. RNA interference studies determined FoxO3a's role in pyroptosis. In vivo efficacy of the miR-150-5p inhibitor was evaluated using HE, Masson staining, and immunofluorescence. RESULTS: In AS tissue exosomes, miR-150-5p levels increased whereas FoxO3a levels decreased. miR-150-5p regulated FoxO3a, enhancing macrophage pyroptosis. The miR-150-5p inhibitor reduced ox-LDL-induced RAW264.7 injury and pyroptosis by improving cell viability, decreasing LDH levels, and downregulating pyroptosis related proteins (Caspase-1, NLRP3, GSDMD-N). FoxO3a knockdown weakened the inhibitor's effects on NLRP3/GSDMD-mediated pyroptosis. In Apoe-/- mice, the inhibitor upregulated FoxO3a/ARC and suppressed pyroptosis signaling. CONCLUSION: This study advances understanding of miR-150-5p-mediated pyroptosis and highlights the potential of miR-150-5p inhibitors in combating AS.