The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and in...The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and influencing vascular remodeling.This review provides a comprehensive synthesis of current knowledge regarding the structural characteristics and functional properties of the CX3CL1/CX3CR1 pathway.This study delves into its specific mechanistic contributions to atherosclerosis,placing particular emphasis on its regulatory influence across diverse cell types,including arterial endothelial cells,smooth muscle cells,and macrophages.Furthermore,the pathway’s integral involvement in both the initiation and progression of atherosclerotic plaques is dissected,highlighting its critical impact on plaque stability and susceptibility to rupture.The review also extends to the pathogenic significance of CX3CL1/CX3CR1 signaling in atherosclerosis-related comorbidities,incorporating the latest advancements in understanding its roles in coronary heart disease,stroke,and other cardiovascular disorders.By critically integrating findings from the extant literature,this review constructs a foundational framework to guide future investigations and underscores the substantial translational potential of targeting this pathway for therapeutic intervention in clinical settings.展开更多
Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin VII(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosi...Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin VII(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.展开更多
基金Study on the Protective Mechanism of Safflower Yellow Pigment on Vascular Endothelial Function in Patients with Phlegm-Stasis Syndrome Coronary Heart Disease and Stable Angina Pectoris(Project No.20222A010012)Single-Cell Immune Panorama Study on Neiguan(PC6)Acupoint Injection for Improving Pyroptosis in Chronic Heart Failure(Project No.2025A03J3499)+1 种基金The study on the effect and mechanism of Guanxinning Tablets on vascular homeostasis and remodeling in populations with early vascular aging(Project No.2024QC-B1007)Guangzhou Key Laboratory of Traditional Chinese Medicine Rehabilitation(Project No.2024A03J0790).
文摘The CX3CL1/CX3CR1 signaling axis is established as a pivotal regulator in the pathogenesis of atherosclerosis,with well-documented roles in orchestrating inflammatory responses,mediating immune cell recruitment,and influencing vascular remodeling.This review provides a comprehensive synthesis of current knowledge regarding the structural characteristics and functional properties of the CX3CL1/CX3CR1 pathway.This study delves into its specific mechanistic contributions to atherosclerosis,placing particular emphasis on its regulatory influence across diverse cell types,including arterial endothelial cells,smooth muscle cells,and macrophages.Furthermore,the pathway’s integral involvement in both the initiation and progression of atherosclerotic plaques is dissected,highlighting its critical impact on plaque stability and susceptibility to rupture.The review also extends to the pathogenic significance of CX3CL1/CX3CR1 signaling in atherosclerosis-related comorbidities,incorporating the latest advancements in understanding its roles in coronary heart disease,stroke,and other cardiovascular disorders.By critically integrating findings from the extant literature,this review constructs a foundational framework to guide future investigations and underscores the substantial translational potential of targeting this pathway for therapeutic intervention in clinical settings.
基金supported by the National Natural Science Foundation of China(Grant No.:81873576)Wenzhou Municipal Science and Technology Bureau,China(Grant No.:Y20220023).
文摘Ferroptosis has been shown to mediate the development of fibrosis.Polyphyllin VII(PP7),a bioactive component of Paris polyphylla,exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis.In this study,treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells(HSCs),which could be suppressed by a ferroptosis inhibitor.In addition,it promoted HSC ferroptosis by suppressing glutathione(GSH)peroxidase 4(GPX4)and enhanced the expression of CX3C chemokine ligand 1(CX3CL1).Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4.Notably,CX3CL1 directly interacted with GPX4,triggering HSC ferroptosis.The transcription factor hypermethylated in cancer 1(Hic1),which binds to the Cx3cl1 promoter,increased the expression of CX3CL1.Its absence resulted in downregulation of CX3CL1,suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation.HIC1 was found to directly interact with PP7 at the GLY164 site.Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes.HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo.These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.
