| Section1:The relationship between Th17cell related inflammatory factors and coronary artery disease andBackgroundIt has been proved by many landmark studies that atherosclerosis is a chronic inflammatory disease. Adaptive immune, which is characterized by the involvement of kinds of lymphocyte, plays a key role in the development of atherosclerosis. Recently, T helper cell17(Th17), which is identified by the secretion of IL-17a, has been focused by researches which presented the critical role of Thl7in the chronic inflammatory disease. IL-6is essential for the differentiation of Th17. IL-6can bind not only the specific receptor on the cell membrane, but also the soluble IL-6receptor (sIL-6R), which originates from shedding of the membrane-bound IL-6receptor by disintegrin and metalloproteinase17(ADAM17). The purpose of this study was to investigate the serum levels of AD AM17, IL-6, sIL-6R, IL-17a, and Th17in patients with coronary artery disease (CAD), research the role of the trans-singling pathway of IL-6in the development of Th17, and reveal the effect of these inflammatory factors on the development of coronary artery disease.MethodsOne hundred and sixty-four patients were enrolled. Coronary angiography was performed in all the patients. According to the results of coronary angiography and the clinical manifestation, patients were divided to3groups as control group (n=65), stable angina group (SA, n=55), and unstable angina group (UA, n=44). The patients with non-ST segment elevated and ST segment elevated myocardial infarction were excluded. The serum levels of ADAM17, IL-6, sIL-6R, and IL-17a were measured by ELISA, and the peripheral levels of Th17were measured by flow cytometry. SYNTAX score was used to assessed the severity of coronary artery disease.ResultsNo difference of serum levels of ADAM17, IL-6, sIL-6R, and IL-17a between groups was found. In the multifactor analysis, the level of IL-17a was associated with the use of β receptor blocker, bit endothelin-1, IL-6, IL-23, and sIL-6R(p=0.002, 0.013,0.007,0.032, and＜0.001; respectively). The level of ADAM17was related with the level of sIL-6R significantly(r=0.919, p<0.001), and an exponential relation was found between them by the curve regression analysis. No significant relationship was found between IL-17a and IL-6in CAD patients. Significant relationship between IL-17a and sIL-6R as well as ADAM17was presented in all groups (all p<0.05).There was no significant difference of the proportions of peripheral Thl7a to Th cell between groups. Multifactor analysis showed that the proportion of Th17a to Th cell was significantly higher in SA and UA groups than in control group (β=0.256,0.263; p=0.028,0.016; respectively), and the proportion was associated with the use of aspirin and β receptor blocker and the history of CAD(p<0.001,=0.002,0.013, respectively). The proportions of peripheral Thl7a to Th cell was related with the serum level of IL-17a and ADAM17(r=0.283,p=0.006). The Th17counts in peripheral blood were calculated. Significant difference of Th17counts was found between groups(p=0.044).There was no significant difference of SYNTAX score between SA and UA groups(r=0.31, p=0.026). The serum level of IL-6was positively related with SYNTAX score. After adjusting age, sex, BMI, hypertension, hyperlipemia, diabetes, smoking, and family history of CAD, the serum of IL-6was still related with SYNTAX score(F=8.709, p=0.006).ConclusionThe serum level of IL-6is related with the severity of coronary artery disease, and the soluble receptor of IL-6may play a role in the differentiation of Th17and the secretion of IL-17a in patients with CAD. As to sIL-6R, the level of ADAM17is related with its level, implying that ADAM17plays a role in origination of sIL-6R. Some drugs including Aspirin and β receptor blocker, as well as the endothelium-related-factor such as endothelin, may also affect the differentiation of Th17and the secretion of IL-17a. Section2:The association between coronary artery disease and Th17cell as well as interleukin17:Meta-analysisBackgroundRecently, a great deal of researches focused on the Th17cell, which is characterized by the secretion of IL-17a. Several studies showed the critical role of Th17cell in several chronic inflammatory diseases, including atherosclerosis. However, studies investigating the relationship between CAD and Th17as well as IL-17got conflicting results. The understanding of the role of Th17and11-17is important for the interpretation of the role of inflammation in the development of CAD. The aim of this study was to The aim of this study was to evaluate the association between CAD and Th17as well as IL-17by conducting a systematic review and meta-analysis.MethodsA systematic search of publications in PubMed, Embase, and the Cochrane Library without language restriction was performed. The following search terms were used:Th17, IL-17, interleukin17, coronary heart disease, coronary artery disease, acute coronary syndrome, myocardial infarction, and angina. Studies were included in the meta analysis if they met the following criteria:(1) cross-sectional design;(2) patients over18yeas were enrolled;(3) patients with CAD were enrolled and divided to following groups according the clinical manifestation:stable angina (SA) group, unstable angina (UA) group, acute myocardial infarction (AMI) group, or acute coronary syndrome (ACS) group;(4) a control group was included;(5) CAD was diagnosed by coronary angiography or computer tomogram;(5) the peripheral serum level of IL-17and/or the proportion of Th17to the total T cell was measured (Th17cell was identified as cell with positive surface antigen of CD3and CD4and intracellular antigen of IL-17.The standardized mean difference (SMD) was used as the measure of effect and the results were expressed as a RR with95%confidence intervals (CIs). The heterogeneity among studies was tested by Q-statistic and I-statistic. Sensitivity analysis was conducted to test the robustness of the results. ResultsTwelve studies with941patients were identified. In the pooled results, the level of serum IL-17in SA group was not higher than the level in control group(SMD=0.66,95%CI-0.06to1.38, p=0.07), but the levels in UA and AMI groups were both elevated compared with control group(SMD=2.81,95%CI0.98to4.64, p=0.003; SMD=2.99,95%CI1.12to4.86,p=0.002). An elevating trend was found between the levels of IL-17in SA, UA, and AMI groups. The level of IL-17in ACS group was significantly higher compared with control and SA groups(SMD=2.19,95%CI1.08to3.30, p＜0.001).The proportions of Thl7cell to CD4+T cell was significantly higher in SA, UA, and AMI groups compared with control group(SMD=1.14,95%CI0.59to1.69, p＜0.001; SMD=5.32,95%CI3.21to7.44, p＜0.001; SMD=5.54,95%CI3.09to7.98, p=<0.001). An elevating trend was found between the levels of Thl7cell in SA, UA, and AMI groups. The proportions of Th17cell to CD4+T cell in ACS group was significantly higher compared with control and SA groups(SMD=3.95,95%CI2.43to5.46, p＜0.001).In the sensitivity analysis, the pooled results were not affected by any single result, implying the robustness of the results.ConclusionThe meta-analysis of related articles showed that Th17cell and IL-17was related with coronary artery disease and its clinical manifestation, implying that they may play a role in the development of coronary atherosclerosis and the unstable state of CAD. Section3:The relationship of Th17cell related inflammatory factors with the pulse wave velocity, ankle-brachial index, and carotid intima-media thicknessBackgroundArterosclerosis has been proven as an risk factor for many cardiaovascular diseases. Many methods have been developed to assess the function and structure of artery tree, such as pulse wave velocity (PWV), intima-media thickness (IMT), and ankle-brachial index (ABI). These indices reflect the changes of function and structure in aorta and peripheral arteries, and can be used to stratify the cardiovascular risk in population without clinical CVD manifestation.Several studies presented that inflammation plays a critical role in the development of arteroseclerosis. The aim of the study was to analyze the association of several inflammatory factors including AD AM17, IL-17a, IL-6, and sIL-6R with the indices of artery functional and structural assessment including PWV, IMT, and ABI.MethodsOne hundred and sixty patients were enrolled. The serum levels of AD AM17, IL-6, SIL-6R, and IL-17a were measured by ELISA. Brachial-ankle PWV (baPWV), ABI, and IMT were measured in these patients. ResultsSignificant correlation of IMT with AD AM17and sIL-6R was showed(r=0.17,0.21,; p=0.027,0.007). No significant correlation of baPWV with ADAM17, sIL-6R, IL-6, IL-17a, and IL-23was found. After the adjustment of age, sex, BMI, hypertension, hyperlipemia, diabetes, smoking, and CAD family history, significant association between IMT and sIL-6R was showed(F=5.394, p=0.022). ConclusionThe level of sIL-6R was associated with the severity of carotid arterosclerosis, implying that it may play a role in the development of arterosclerosis. Section4:The relationship between brachial-ankle pulse wave velocity and severity of coronary artery disease measured as SYNTAX scoreBackgroundAortic stiffness is the independent predictor for cardiovascular events. Carotid-femoral pulse wave velocity (cfPWV) has been recommended as the gold-standard to access the aortic stiffness. Brachial-ankle pulse wave velocity (baPWV) uses the pulse wave in brachial and ankle artery to access the aortic stiffness which is a more convenient and less time-consuming method compared with cfPWV. Pervious studies proved the correlation between cfPWV and baPWV, and the latter was also an independent predictor for cardiovascular events. cfPWV was presented with relationship with the anatomic severity of CAD. We hypothesized that baPWV is also associated with the severity of CAD. The aim of this study was to evaluate the association between aortic stiffness measured as baPWV and severity of coronary artery disease measured as SYNTAX score.MethodsFour hundred and three patients who underwent primary angiography as well as baPWV were enrolled. SYNTAX scores were assessed according to the angiographic results. Patients were divided to three groups according to the results of coronary angiography:control group (no≥50%stenosis in major coronary artery), low SYNTAX group, and high SYNTAX group. Ordinal logistic regression analysis was used to evaluate the association between cfPWV and SYNTAX score.ResultsA significant difference of baPWV was found between groups(p=0.040). After adjusting for age, body mass index, smoking, family history of cardiovascular diseases, blood pressure, total cholesterol, and high-density lipoprotein cholesterol, baPWV was associated with the SYNTAX score(OR=1.10,95%CI:1.01-1.21, p=0.038).ConclusionAortic stiffness measured as baPWV was associated with SYNTAX score, which provides useful information for predicting the anatomic severity of coronary atherosclerosis. |
PDF Full Text Request