Combination of rosuvastatin and probucol inhibits MMP-9 expression via upregulation of miR-497 in cultured HUVECs and apoE knockout mice.
This study deciphered the molecular mechanisms of the inhibition of MMP-9 expression using rosuvastatin in cultured human umbilical vein endothelial cells (HUVECs) and apoE knockout mice and whether the combination of rosuvastatin and probucol enhanced this effect. The role that microRNA (miR)-497 plays in the regulation of MMP-9 expression was evaluated in cultured HUVECs and apoE knockout mice using quantitative real-time reverse transcription polymerase chain reaction and Western blotting. First, TNFα significantly increased mitogen-activated protein kinases/extracellular signal-regulated kinase (MAPK/ERK) signaling and MMP-9 levels, and the transfection of miR-497 prevented this increase. The converse results were obtained after miR-497 suppression. Second, the administration of rosuvastatin or the combination of two drugs decreased MAPK/ERK signaling and MMP-9 levels, and the suppression of miR-497 upregulated these levels. Third, the administration of rosuvastatin or the combination of two drugs increased miR-497 expression levels in the aortas of apoE knockout mice, but the levels of serum lipids and plaque areas decreased, which improved plaque components and decreased the MAPK/ERK signaling and MMP-9 levels. Finally, the combination of the two drugs was more effective than the use of rosuvastatin alone. Rosuvastatin inhibits MMP-9 expression by upregulating miR-497 in HUVECs and apoE knockout mice, and the combination of rosuvastatin and probucol enhances this effect.
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-Yuan
YY
Wang
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.
Hui
H
Li
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.
Xing-Hua
XH
Wang
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.
Meng
M
Yuan
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. tjcardiol@126.com.
Guang-Ping
GP
Li
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D011341:Probucol / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium / Q000494:pharmacology*
D001057:Apolipoproteins E; C559640:MIRN497 microRNA, human; D035683:MicroRNAs; C550139:mirn497 microRNA, mouse; D000068718:Rosuvastatin Calcium; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D011341:Probucol
Matrix metalloproteinases; MicroRNAs; Probucol; Rosuvastatin