Study On The Association Of CXCL16/CXCR6 With Carotid Atherosclerosis Of Metabolic Syndrome

Background:Metabolic syndrome(MS) is a clustering of some cardioavascular risk factors,including obesity,hypertension,hyperglycemia and dyslipidemia.With the development of society and changes of life style,the prevalence of MS is increased.The pathogenesis of atherosclerosis of MS is very complex,and it is now considered that many dangerous factors of cardiovascular disease exist in the MS meanwhile,these factors interreative and influnce,therefore form vicious circle,though the funtion to the arteries system,lead to artery-intima damage,endothelia funtion disorder,in the end form the artery plaque.More and more studies indicated that atherosclerosis is an inflammatory disease,immune impairment involved in the initiation and progression of atherosclerosis.Epidemiology and animal experiments demonstrated that T lymphocyte cells are the most important effective cells in the immune response.Chemokine is a group of cytokines that have the function of chemotaxis,whose main function is to attract immune cells to the area of immune responses,meanwhile attend immune adjustment and immune pathological reaction.A novel Chemokines Cxc116 was found in the rencent years,A series of studies conducted described cxc116/SR-PSOX-a new molecule combining three funtions:Chemokines,scavenger receptor and adhesion molecules,as an adhesion molecules,cxc116/SR-PSOX might mediate T cell adhesion to the endothelium;as a Chemokine-drive T cell migration,stimulate cell proliferation and elicit inflammatory phenotype in SMC and,finally,as a scavenger receptor-mediate uptake of atherogenic lipoprotein by macrophages and SMC.All these effects are known to be pro-atherogenic.Chemokines play role through combining with Chemokine receptors,Cxcr6 is the only knownChemokine receptor for cxc116,which is mainly expressed on Tcells,B cells,NKT cells and DC.Chemokine experiment demonstrated that only the cells that highly expressed cxcr6,can it have immune responses.The relation of cxc116/cxcr6 and atherosclerosis was gradually known by people,but the study nowadays is animal experiments,there are few reports referring to the relationship between cxc116/cxcr6 and atherosclerosis of MS.Therfore,we carried out the present study and tried to find the evidences of cxc116 /cxcr6 and atherosclerosis.Objectives:Study on the association of cxc116/cxcr6 with carotid atherosclerosis of metabolic syndromeSubjects:In our study,we recruited 60 consecutive subjects with 30 carotid arteries plaque of MS and 30 age-and - sex matched normal subjects without cardiovascular diseases or diabetes mellitus.Methods:All subjects completed a questionnaire on present condintion,family and medical histories of cardiovascular risk factors and complication,waist circumference and blood press(BP) were measured.Furthermore,fasting blood sample was collected from each subjects after 12-14 hours fast to determine the fasting blood glucose(FBG),triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C).The cxc116mRNA and cxcr6mRNA were detected using Real-Time Quantitative Reverse Transcriptase-Polymerase Chain Reaction(RT-PCR)methods.The activation of T lymphocyte cells,the expression of cxcr6 on the T lymphocyte cells and natural killer T cells was dected using Flow Cytometry.The serum level of sol-cxc116 and IFN-γwas determined using ELISA.Results:(1) Compared with controls,the MS group showed significantly higher waist circumference,cholesterol,triglyceride and LDL-C(p＜0.001,respectively).The mean IMT,maximum IMT,Ds,Dd,plaque index of the MS group were significantly higher than those of the control group(p＜0.001,respectively).Furthermore,the MS group showed significantly decreased in Vs,Vd,RI and AC(p＜0.001,respectively),with significantly increases in PI,EP,β(p＜0.001,respectively).(2) Waist circumference,blood press,TG significantly correlated with mean IMT,maximumIMT,plaque index,Ds and Dd(p＜0.05,respectively),which denoted the structure of the carotid artery.Meanwhile Waist circumference,blood press,TG significantly correlated withVs,Vd,RI,AC,EP,EP*(p＜0.05,respectively),which denoted the function of the carotid artery.(3) Compared with controls,the levels of sol-cxc116 and cxc116mRNA of MS group showed significantly higher,Furthermore it correlated with maximumIMT,plaque index(p＜0.05,respectively),which denoted the structure of the carotid artery.(4) Compared with controls,the activation of CD3+T lymphocyte cells,CD4+ T lymphocyte cells of MS group showed significantly higher,Furthermore it correlated with maximumIMT,plaque index(p＜0.05,respectively),which denoted the structure of the carotid artery.(5) Compared with controls,the expression of cxcr6+T T lymphocyte cells,cxcr6+NKT cells showed significantly higher,Furthermore it correlated with maximumIMT,plaque index(p＜0.05,respectively),which denoted the structure of the carotid artery.Conclusions:(1) Alterations to carotid arteries of the MS patients Significant thickened IMT,increased plaque index,distended vesseldiameter,reduced elasticity and augmented stiffness.(2) Waist circumference,blood press,TG are independent risk factors for damaging carotid structure and functionof MS patients.(3) Cxc116 in the peripheral blood of carotid atherosclerosis of MS is significantly higher,furthermore it is correlated with maximum IMT,plaque index(p＜0.05,respectively),which denoted the structure of the carotid artery.It suggested that cxc116 attended the formation of carotid atherosclerotic plaue of MS.(4) The expression of cxcr6 in the T cells,NKT cells is significantly higher in carotid atherosclerosis of MS,furthermore it is correlated with maximumIMT,plaque index(p＜0.05,respectively),which denoted the structure of the carotid artery.It suggested that cxcr6 attended the formation of carotid atherosclerotic plaue of MS.(5) The activation of T cells is significantly higher in carotid atherosclerosis of MS,furthermore it is correlated withmaximumIMT,plaque index(p＜0.05,respectively),which denoted the structure of the carotid artery.It suggested that T cells is the important effevtive cells in the pathogenesis of atherosclerosis.