【摘 要】
：
Farnesoid X receptor (FXR),a member of the nuclear receptor superfamily of ligand-activated transcription factors,plays an important role in the regulation of lipid homeostasis.Activation of FXR has b
【机 构】
：
Zhejiang Provincial Hospital of Traditional Chinese Medicine
【出 处】
：
2016年浙江省医学会心电生理与起搏学术年会
论文部分内容阅读
Farnesoid X receptor (FXR),a member of the nuclear receptor superfamily of ligand-activated transcription factors,plays an important role in the regulation of lipid homeostasis.Activation of FXR has been reported to attenuate atherosclerosis development.However,its molecular mechanism remains unclear.In this study,we analyzed the effects of the FXR agonist GW4064 on macrophage apoptosis in atherosclerosis.We showed that GW4064 significantly improved plasma blood LDL-C levels and reduced atherosclerosis development by HE staining.Moreover,we found by that GW4064 reduced macrophage infiltration and repressed macrophage apoptosis both in vitro by flow cytometry and in atherosclerosis plaques with APOE-/-mice.Western blot and real time PCR results revealed that GW4064 significantly decreased Fas/FasL levels,which are involved in plaque instability in humans.Finally,we discovered that GW4064 downregulated PCSK9 and upregulated LDLR levels,which also play important roles in LDL-C regulation and macrophages apoptosis.In summary,our findings demonstrated that GW4064 attenuated the atherosclerosis development,which was related with the repressed macrophages apoptosis and down-regulated of PCSK9 expression.
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