Morin,a matrix metalloproteinase 9 inhibitor,attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling  

作　　者：Yuan He Xiao-xuan Qin Ming-wei Liu Wei Sun 

机构地区：[1]Department of Cardiology,Jiangsu Provincial People’s Hospital,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China [2]Department of Neurology,Jiangsu Provincial People’s Hospital,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China

出　　处：《Journal of Integrative Medicine》2024年第6期683-695,共13页结合医学学报（英文版）

基　　金：supported by grants from the National Key R&D Program of China(No.2019YFA0210100);the Young Scholars Fostering Fund of the First Affiliated Hospital of Nanjing Medical University(No.PY2022010[NP22])。

摘　　要：Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(End MT)in atherosclerosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medicine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing End MT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro End MT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/m L)for 48 h.The in vivo experiments were performed in an atherosclerosis model using apolipoprotein E(Apo E)^(-/-)mice fed with a high-fat diet(HFD).Mice in the intervention group were given morin(50 mg/kg)orally for 4 weeks.Molecular docking and microscale thermophoresis were assayed to understand the interactions between morin and matrix metalloproteinase-9(MMP-9).Results:Morin inhibited the expression of End MT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 signaling in TGF-β1-induced End MT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on End MT.In the HFD-induced atherosclerotic Apo E^(-/-)mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing End MT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt End MT in atherosclerosis by limiting the activation of Notch-1 signaling.This study underscores morin's potential utility in the development of antiatherosclerotic medication.

关 键 词：MORIN Endothelial-to-mesenchymal transition ATHEROSCLEROSIS Traditional Chinese medicine Matrix metalloproteinase-9 

分 类 号：R543.5[医药卫生—心血管疾病]