Interfering microRNA-410 attenuates atherosclerosis via the HDAC1/KLF5/IKBα/NF-κB axis

MicroRNA (miR)-410 plays a potential role in the pathogenesis of atherosclerosis. The current study mainly focuses on the underlying mechanism of miR-410/histone deacetylase 1 (HDAC1)/KLF5/nuclear factor kappa B (NF-kappa B) inhibitor alpha (IKB alpha)/NF-kappa B axis in atherosclerosis. miR-410 expression was determined using quantitative real-time PCR in both mouse models of atherosclerosis and human umbilical endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (ox-LDL). The study subsequently predicted regulators associated with miR-410 through bioinformatics, and their binding relation was further verified through dual luciferase reporter gene and RNA immunoprecipitation (RIP) assays, and how HDAC1 regulated KLF5 was tested through coimmuno-precipitation (coIP). In HUVECs, miR-410 and HDAC1 mRNA expression; HDAC1, KLF5, IKB alpha, p65, p-p65, VCAM-1, ICAM-1, and MCP-1 protein expression; and inflammatory cytokine expressions were detected using quantitative real-time PCR, western blot, and ELISA. The present study further tested cell functions by Cell Counting Kit-8 (CCK-8), flow cytometry, and the colony-formation assay. It was revealed that miR-410 could target HDAC1, whereas HDAC1 could target transcription factor KLF5, increasing IKB alpha expression, thus suppressing NF-kappa B in atherosclerosis. Furthermore, silencing miR-410 or overexpressing HDAC1 increased cell viability and suppressed apoptosis and an inflammatory reaction in HUVECs in atherosclerosis. Blocking miR-410 promotes HDAC1 expression and increases IKB alpha levels through KLF5 to suppress NF-kappa B, thus preventing development of atherosclerosis.

Automated summary

The study revealed that miR-410 targets HDAC1 to suppress NF-kappa B pathway in atherosclerosis, indicating a potential therapeutic target for preventing atherosclerosis development.