Effect of ezetimibe on atherosclerosis induced by advanced glycation end products
WEI Xin-ji
SHI Min
XIA Jin-qing
YU Wan-shui
Abstract：Objective:To study the effect of ezetimibe(EZE)on atherosclerosis induced by advanced glycation end products(AGEs).Methods:The atherosclerotic model rats were purchased and divided into the model group and the treatment group with 10 rats each using random number method.After 8 weeks of EZE treatment in the treatment group,the changes of aortic tissue and protein expression in the two groups were analyzed.The cultured rat thoracic smooth muscle cells(VSMC)were divided into control group,AGEs group,EZE group and combined treatment group,and the expression level of specific protein was analyzed.Calcium content in cells was detected by calcium detection reagent and Von Kossa staining.Finally,cell proliferation capacity and integrin-linked kinase(ILK)signaling pathway were examined.Results:HE staining revealed thinning of the intima and mid-membrane in the arterial tissue of the model rats after EZE treatment.Immunohistochemical staining showed an increase in the number of α-SMA-positive cells and a decrease in the number of OPN-positive cells in the intima-media of the arteries after EZE treatment(P<0.05).EZE improved the pathological structure of the aorta in model rats,with elevated cell surface α-smoothmuscleactin(α-SMA)and reduced expression of osteopontin(OPN)(P<0.01).After treatment of vascular smooth muscle cells with AGEs,the expression of α-SMA was decreased,the expression of OPN,alkaline phosphatase(ALP)and proliferating cell nuclear antigen(PCNA)was increased,and the cytoplasmic calcium content of cells was increased;the expression of α-SMA was increased,the expression of OPN,ALP and PCNA was decreased,and the cytoplasmic calcium content of cells was decreased in the co-treated group(P<0.01).AGEs activated the ILK/mammalian target of rapamycin(mTOR)signalling pathway in vascular smooth muscle cells,whereas EZE significantly inhibited the activation of the ILK/mTOR signalling pathway.Conclusion:AGEs play a key role in the occurrence and development of renal atherosclerosis,but EZE can improve the development of AGEs-induced atherosclerosis by inhibiting the ILK/mTOR signaling pathway.
Keywords：EzetimibeAtherosclerosisIntegrin-lindedkinase/mammalian target of rapamycinAdvanced glycation end productsVascular smooth muscle cell
Publication Date：2023-12-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 422-426 )