Abstract: BACKGROUND:MicroRNAs (miRNAs) have emerged as crucial players in the initiation and development of atherosclerosis (AS), and the low miR-223-3p level is observed in AS patients. However, the function and mechanism behind miR-223-3p in AS progression have not been fully elucidated. METHOD:In the present study, THP-1 cells treated with oxidized low-density lipoprotein (ox-LDL) were employed as the cell model of AS. The expression levels of miR-223-3p, NLR family pyrin domain containing 3 (NLRP3), caspase-1, pro-caspase-1, cleaved interleukin 18 (IL-18), cleaved IL-1β, and forkhead box O3 (FOXO3) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB) analyses. The relationship between miR-223-3p and FOXO3 or NLRP3 was determined using a dual-luciferase reporter assay. The production of IL-1β, IL-18, IL-6, and TNF-α was examined by Enzyme-linked immunosorbent assay (ELISA). RESULTS:MiR-223-3p was decreased in AS patients and ox-LDL-induced THP-1 cells, and its upregulation downregulated the abundance of NLRP3, caspase-1, cleaved IL-18, cleaved IL-1β, IL-1β, IL-6, and TNF-α in THP-1 cells treated with ox-LDL or not, and the depletion of miR-223-3p revealed an opposite phenomenon. NLPR3 and FOXO3 were identified as two authentic targets of miR-223-3p. Knockdown of NLRP3 or FOXO3 reversed the stimulatory effect of the miR-223-3p inhibitor on the inflammatory responses of THP-1 cells. CONCLUSIONS:Our data indicate that miR-223-3p inhibited ox-LDL-mediated NLRP3 inflammasome activation via directly targeting NLRP3 and FOXO3 in THP-1 cells, which offered a prospective therapeutic target for AS therapy.
