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

Autor: Wang YY; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China., Li H; Department of Endocrinology and Metabolism, General Hospital of Tianjin Medical University, Tianjin 300052, People's Republic of China., Wang XH; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China., Yuan M; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China., Li GP; Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Tianjin Institute of Cardiology, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, People's Republic of China. Electronic address: tjcardiol@126.com.
Jazyk: angličtina
Zdroj: Thrombosis research [Thromb Res] 2016 Apr; Vol. 140, pp. 51-58. Date of Electronic Publication: 2016 Feb 12.
DOI: 10.1016/j.thromres.2016.02.012
Abstrakt: Objective: This 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 Methods: We 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.
Results: First, 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).
Conclusions: Probucol inhibits MMP-9 expression through regulating miR-497 in HUVECs and apoE knockout mice.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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