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Roles Of Serum CXC Chemokines In Coronary Atherosclerotic Heart Disease And Coronary Slow Flow Phenomenon

Posted on:2018-04-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y F LiangFull Text:PDF
GTID:1314330542483462Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Background Coronary atherosclerotic heart disease(CHD)is a common and frequently occurring disease which seriously endangers human health.The incidence of CHD is a complex pathophysiological process,including atherosclerosis(AS),thrombosis,coronary spasm and so on.In recent years,the incidence of coronary heart disease increased year by year,and become an important cause of death,now that atherosclerosis is a chronic inflammatory disease and lipid metabolism disorders,involving the artery wall,pathology showed accumulation of extracellular matrix and lipid,inflammatory cells,such as macrophages,T lymphocytes and smooth muscle cells.Clinical studies have shown that inflammatory and immunological mechanisms play an important role in the development of atherosclerotic plaque rupture and thrombosis.In the area of atherosclerotic plaque has obvious infiltration of activated macrophages,T lymphocytes and mast cells,these cells secrete cytokines,growth factors,chemokines play an important role in the pathogenesis of atherosclerosis.It has been proved that chemokines play an important role in the activation and migration of inflammatory cells,which is an important factor in the progression of atherosclerosis.With the development and popularization of coronary angiography,coronary angiography was performed in patients with angina pectoris,and abnormal coronary flow and coronary slow flow phenomenon(CSFP)were detected.The detection rate was about 7%.So far,the pathogenesis of CSFP is not clear,and the treatment for CSFP is in the experimental stage.On the other hand,a number of studies have shown that patients with slow blood flow slowed down the blood circulation and cause symptoms such as angina,coronary heart disease slow blood flow and inflammation are closely related.CXCL9 is a non ELR chemokine,also known as interferon inducible monocyte factor(MIG),which plays an important role in the stabilization of blood vessels in vivo.Animal experiments show that CXCL9 has the effect of inhibiting angiogenesis.As the only receptor of CXCL9,CXCR3 belongs to the G protein coupled receptor superfamily,which is mainly expressed in T lymphocytes and NK cells.CXCR3 can be coupled with G protein and can be expressed in mouse bone marrow cells stimulated by IL-2.In addition,m RNA expression of CXCR3 can be detected in CD34 progenitor cells.In the specific mechanism,chemokine CXCL9 chemotaxis is mainly mediated by CXCR3,CXCR3 and CXCL9 combined activation can improve the level of Src phosphorylation and activation of Src kinase activity,and activation of phosphatidylinositol 3 kinase(PI3K)signaling pathway play a regulatory role.The results indicate that CXCL9/MIG can be used as a biomarker of inflammation and atherosclerotic plaques in human T cells.After adjusting the predisposing factors and drug application effect of precursor,the level of circulating MIG/CXCL9 and carotid artery intima-media thickness of the independent,this finding suggests that MIG in the early development of atherosclerosis has potential significance for prediction.In the adjustment of traditional cardiovascular risk factors,serum MIG/CXCL9 level and coronary artery calcification(CACS)independently,but the role of CXCL9/MIG in coronary artery disease and whether in coronary slow flow play a role,there are few reports.Purpose In this study,patients with coronary heart disease(CHD)were selected as the research object,and the role of CXCL9 in coronary heart disease(CHD)was studied in two parts.To reveal the relationship between CXCL9 and coronary heart disease and coronary slow flow,and provide theoretical basis for the treatment of coronary heart disease and coronary slow blood flow to provide new molecular targets.Method1)The patients were selected because of chest pain and other symptoms and hospitalization,clinically diagnosed as coronary heart disease,CAG examination of patients as parallel operation as the object of study(197 cases),of which 117 cases were diagnosed by CAG for the diagnosis of coronary artery disease(CHD group),80 cases with CAG to exclude the diagnosis of coronary heart disease patients(non CHD group).According to the results of CAG,the CHD group patients were divided into three groups: 1)vessel disease(46 cases),2 vessel disease(39 cases)and multivessel disease(32 cases).The severity and extent of CAD were evaluated according to the Gensini score.2)The patients with no coronary artery stenosis(stenosis or stenosis < 40%)were selected,and the diagnostic TIMI frame correction method for CSFP patients with 46 cases as the coronary slow flow group(CSFP group),randomly selected CAG patients with normal coronary blood flow in 50 cases as normal group(CSFP group,NCF).The coronary blood flow was calculated.3)The patients general information(age,gender,smoking history and history of disease,BMI),and conventional BNP,blood lipid,fasting blood glucose,blood uric acid and high sensitive C reactive protein,homocysteine and other factors determine the level of etc.,were collected and recorded.4)To measure the serum concentration of inflammatory factor,blood samples were centrifuged within 1 h of collection.The blood of patients with 5ml,3000 rpm speed centrifuge for 15 minutes to separate serum,in-80 C refrigerator frozen batch inspection,this experiment using double antibody sandwich ELISA assay for serum samples of CD40 L,IFN-,CXCL9 and gamma inflammatory cytokines IL-1,IL-6 and IL-10 level.5)The basic data difference were analyzed and compared of the CHD group and no CHD group,forexample,serum biochemical indexes,heart rate,BNP and CD40 L,IFN-γ,CXCL9 levels.The basic data difference were analyzed and compared of patients with coronary heart disease group(three subgroups).The levels of BNP and CD40 L,IFN-γ,CXCL9 were analyzed and compared,through single factor and multi factor regression analysis on the correlation between serum CXCL9 levels and coronary heart disease and the severity of coronary heart disease,further application of logistic multivariate analysis in serum CXCL9 level is an independent risk factor for coronary heart disease progression.6)To compare the difference between CSFP group and non CSFP group,such as the general data,serum biochemical parameters,cardiac hyper,BNP and CXCL9 levels,and to analyze the correlation between the coronary slow flow and the level of CXCL9 in serum.Result1)The serum levels of CD40 L,IFN-and CXCL9 in patients with coronary heart disease were significantly higher than those in non CHD group(p<0.05).2)The levels of CD40 L,IFN-and CXCL9 in serum of patients with multivessel disease were significantly higher than those in the 1 vessel disease group and the 2 vessel disease group(p<0.05)in the subgroup of patients with coronary artery disease(p<0.05).3)Further statistical analysis showed that the level of CXCL9 in serum and the severity of coronary heart disease have significant positive correlation,the serum CXCL9 level is an independent risk factor for CHD progression.4)The level of serum CXCL9 in CSFP group was significantly higher than that in NCF group(p<0.05),and further statistical analysis showed that CSFP was positively correlated with the level of CXCL9 in serum.5)Multivariate Logistic regression analysis showed that CXCL9 was an important risk factor for CSFP.Conclusion In our study,we analyzed the role of CXCL9 in patients with coronary heart disease,and studied its relationship with CSFP:1)There has a significant correlation between serum CXCL9 level and coronary heart disease and the severity of coronary heart disease,elevated serum CXCL9 level is an independent risk factor for coronary heart disease exacerbations;2)The level of CXCL9 in serum and CSFP has significant correlation,high levels of serum CXCL9 is an independent risk factor for coronary heart disease with CSFP;3)CXCL9 may be more of the expression of inflammatory cytokines,increased vascular inflammatory reaction,and then participate in the occurrence and development of coronary atherosclerosis and CSFP.
Keywords/Search Tags:Atherosclerosis, chd, CXCL9, chemokine, CSFP
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