Probucol inhibits MMP-9 expression through regulating miR-497 in HUVECs and apoE knockout mice

- Probucol increased miR-497 expression in HUVECs and apoE knockout mice.
- Probucol decreased serum lipid levels, decreased MAPK/ERK signaling and decreased MMP-9 levels in apoE knockout mice.
- Probucol inhibits TNFα-stimulated MMP-9 expression via upregulation of miR-497 in HUVECs and apoE knockout mice.
- Probucol increased HDL levels while lowering TC and LDL levels in apoE knockout mice.

ObjectiveThis study investigated the molecular mechanisms underlying the inhibition of MMP-9 expression by probucol, which is widely used for atherosclerotic prevention, in cultured human umbilical vein endothelial cells (HUVECs) and apoE knockout mice.Materials and methodsWe used three target scan algorithms and observed that microRNA (miR)-497 targeted MEK1, a member of the MAPK/ERK signaling involved in regulating MMP-9 expression. HUVECs were treated with TNFα, and apoE knockout mice were fed a high-fat/high-cholesterol diet with or without probucol pretreatment. We focused on the association between miR-497 and MAPK/ERK signaling and MMP-9 expression.ResultsFirst, miR-497 expression was significantly higher in the probucol-treated HUVECs and apoE knockout mice compared with non-probucol-treated HUVECs and apoE knockout mice (both p < 0.05). Second, MAPK/ERK signaling and MMP-9 levels were downregulated in probucol-treated HUVECs that were treated with TNFα (p < 0.01), while MAPK/ERK signaling and MMP-9 levels were upregulated after suppression of miR-497 (p < 0.01). Third, probucol increased miR-497 expression levels in the aortas of apoE knockout mice (p < 0.05) while decreasing the levels of serum lipids and plaque areas (p < 0.05), which decreased the MAPK/ERK signaling and MMP-9 levels (p < 0.05).ConclusionsProbucol inhibits MMP-9 expression through regulating miR-497 in HUVECs and apoE knockout mice.