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  • Title: Paeonol Inhibits Oxidized Low-Density Lipoprotein-Induced Vascular Endothelial Cells Autophagy by Upregulating the Expression of miRNA-30a.
    Author: Li C, Yang L, Wu H, Dai M.
    Journal: Front Pharmacol; 2018; 9():95. PubMed ID: 29472864.
    Abstract:
    Paeonol from Cortex Moutan root is a potential therapeutic agent for atherosclerosis (AS). However, its mechanisms of action are still not fully understood. Vascular endothelial cells (VECs) autophagy plays a vital role in the initiation and progression of AS. In this study, we aim to investigate whether the protective effect of paeonol on ox-LDL-induced VECs injury by regulating autophagy. To address this question, we used ox-LDL-induced rat VECs as a model system to elucidate the protective effect of paeonol on VECs injury. This study displayed that ox-LDL (100 mg/L) treatment inhibited VEC growth in dose- and time-dependent manners, paeonol (60 μM) shown potential in inhibiting ox-LDL-induced death. Furthermore, paeonol significantly reduced ox-LDL-induced the formation of autophagy vacuoles and the expression of LC3II in VECs. Further double-luciferase reporter assay shown that miR-30a specifically binds to the 3'-UTR of Beclin-1 mRNA in VECs. Moreover, we found that ox-LDL decreased miR-30a and increased Beclin-1 expression, pretreatment with paeonol could reverse the process of regulation in dose-dependent manners. In ox-LDL treated VECs, transfection with a miR-30a mimic significantly increased miR-30a expression and inhibited Beclin-1 and LC3II expression, thus enhanced the protective effects of paeonol. Whereas transfection with a miR-30a inhibitor significantly decreased miR-30a expression and increased Beclin-1 and LC3II expression, thus attenuated the protective effects of paeonol. In conclusion, this study has, for the ?rst time, highlighted that miR-30a might be a critical target of paeonol against ox-LDL-induced VECs injury by inhibiting excessive autophagy. Paeonol may be one of promising candidate drug for treatment of AS.
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