首页|Morin,a matrix metalloproteinase 9 inhibitor,attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling
Morin,a matrix metalloproteinase 9 inhibitor,attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling
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Morin,a matrix metalloproteinase 9 inhibitor,attenuates endothelial-to-mesenchymal transition in atherosclerosis by downregulating Notch-1 signaling
Objective:Atherosclerotic cardiovascular disease poses a significant health challenge globally.Recent findings highlight the pivotal role of the endothelial-to-mesenchymal transition(EndMT)in atheroscle-rosis.Morin is a bioflavonoid mainly extracted from white mulberry,a traditional Chinese herbal medi-cine with anti-inflammatory and antioxidant properties.This study examines whether morin can alleviate atherosclerosis by suppressing EndMT and seeks to elucidate the underlying mechanism.Methods:We induced an in vitro EndMT model in human umbilical vein endothelial cells(HUVECs)by stimulating the cells with transforming growth factor-β1(TGF-β1)(10 ng/mL)for 48 h.The in vivo exper-iments were performed in an atherosclerosis model using apolipoprotein E(ApoE)-/-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 EndMT markers in a dose-dependent manner in TGF-β1-treated HUVECs.Administering 50 μmol/L morin suppressed the upregulation of MMP-9 and Notch-1 sig-naling in TGF-β1-induced EndMT.Moreover,the overexpression of MMP-9 activated Notch-1 signaling,thereby reversing morin's inhibitory effect on EndMT.In the HFD-induced atherosclerotic ApoE-/-mice,morin notably reduced aortic intimal hyperplasia and plaque formation by suppressing EndMT.Furthermore,morin demonstrated a strong binding affinity for MMP-9.Conclusion:Morin acts as an MMP-9 inhibitor to disrupt EndMT in atherosclerosis by limiting the activa-tion of Notch-1 signaling.This study underscores morin's potential utility in the development of anti-atherosclerotic medication.
MorinEndothelial-to-mesenchymal transitionAtherosclerosisTraditional Chinese medicineMatrix metalloproteinase-9
Yuan He、Xiao-xuan Qin、Ming-wei Liu、Wei Sun
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Department of Cardiology,Jiangsu Provincial People's Hospital,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China
Department of Neurology,Jiangsu Provincial People's Hospital,Nanjing Medical University,Nanjing 210029,Jiangsu Province,China
Morin Endothelial-to-mesenchymal transition Atherosclerosis Traditional Chinese medicine Matrix metalloproteinase-9
NETL
NSTL
万方数据
