Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low-density lipoprotein (ox-LDL), and an AS mouse model was generated with the help of ApoE mice using a high-fat diet regimen. The expression patterns of peroxisome proliferator-activated receptor γ (PPARγ), nuclear factor κB (NF-κB)/p65, miR-19b and histone deacetylase 3 (HDAC3) were then characterized by reverse transcription quantitative polymerase chain reaction and Western blot analysis. In addition, the relationship among PPARγ, NF-κB/p65, miR-19b and HDAC3 was evaluated by co-immunoprecipitation, chromatin immunoprecipitation and dual-luciferase reporter gene assays. Gain- and loss-of-function experiments were also performed to examine their functional significance on ox-LDL-induced inflammation in HUVECs. Enzyme-linked immunosorbent assay was applied to determine the expression patterns of inflammatory factors in AS mice.
PPARγ and HDAC3 were poorly expressed, while miR-19b and NF-κB/p65 were highly expressed in ox-LDL-induced HUVECs and arterial tissues of AS mice. PPARγ inhibited ox-LDL-induced inflammation in HUVECs by ubiquitination and degradation of NF-κB/p65. miR-19b, downregulated by HDAC3, targeted PPARγ and negatively-regulated its expression. Upregulated PPARγ or HDAC3 or downregulated miR-19b or NF-κB/p65 reduced TNF-α and IL-1β expression levels in ox-LDL-induced HUVECs and AS mice.
Collectively, the results show that HDAC3 upregulation prevents inflammation to inhibit AS by inactivating NF-κB/p65 via upregulation of miR-19b-mediated PPARγ, providing a basic therapeutic consideration for AS treatment.
Copyright © 2021. Published by Elsevier B.V.