Inflammatory Cytokines, Arteritis And Aortic Dissection Association Studies

BackgroundTakayasu arteritis (TA) is a chronic nonspecific granulomatous vasculitis affecting aorta and its main branches, coronary, and pulmonary arteries. TA has a characteristic of heterogeneity in ethnic population, regional, age and gender distribution. Multiple factors may be involved into the pathogenesis of TA including autoimmunity, inflammation, genetic and environmental factors and so on. Interleukin-18(IL-18) is an important proinflammatory cytokine with multiple biological functions. It is associated with anti-tumor, anti-inflammatory and autoimmune processes. IL-18gene polymorphism is related to many inflammatory and autoimmune diseases. Numerous studies have showed that IL-18gene exon upstream promoter region-137G/C and-607C/A gene polymorphisms could significantly affect the transcription levels of IL-18, and thus change its expression levels and plasma concentrations. Plasma IL-18levels were significantly higher than normal, and active state of TA showed higher IL-18levels comparing with quiescent state. However, the correlation analysis between-137G/C and-607C/A gene polymorphisms and TA is now lacking. In addition, higher incidence of TA is showed in Chinese population, and thus, Chinese has the convenience in enrolling more TA patients. Therefore, we hypothesized that-137G/C and-607C/A gene polymorphism may be associated with TA, and this correlation may further provide genetic evidence for the pathogenesis of TA.ObjectiveThe aim of this study was to investigate IL-18gene promoter region-137G/C and-607C/A gene polymorphisms, and demonstrated the association of these two gene polymorphisms with TA in Chinese Han population.MethodsThis study enrolled200patients with TA as case group, and334region, age and gender matched healthy subjects as controls. In order to indicate the relationships between IL-18gene polymorphisms and pathogenesis of TA, we genotyped the allele and genotype by using TaqMan probe produced by American ABI company at positions of-137G/C and-607C/A of IL-18gene, and analyzed the distribution frequency, respectively. In the meanwhile, we also compared the frequency about these two position between active and quiescent state of TA.ResultsG/C polymorphism and GG, GC, CC genotypes were identified at position-137of IL-18. C/A polymorphism and CC, CA, AA genotypes were identified at position-607of IL-18gene. Before adjusting risk factors, under dominant, additive, and recessive models, the crude odds ratios (ORs) and95%confidence interval (CI) at position-137G/C were1.658,1.164-2.361(P=0.005);1.554,1.185-2.039(P=0.001);2.141,1.150-3.986(P=0.016), respectively. After adjusting risk factors, under dominant, additive, and recessive models, the adjusted ORs and95%CI at position-137G/C were1.571,1.068-2.311(P=0.022);1.467,1.086-1.980(P=0.012);1.815,0.901-3.656(P=0.095), respectively. As far as the position of-607C/A of IL-18gene was concerned, before adjusting risk factors, under dominant, additive, and recessive models, the crude ORs and95%CI at position-607C/A were0.532,0.406-0.851(P=0.005);0.320,0.568-0.928(P=0.011);0.294,0.481-1.154(P=0.188), respectively. After adjusting risk factors, under dominant, additive, and recessive models, the adjusted ORs and95%CI at position-607C/A were0.533,0.391-0.880(P=0.010);0.266,0.586-1.002(P=0.051);0.122,0.552-1.420(P=0.613), respectively. Moreover, whether under dominant, additive, and recessive models or not, we found no statistical difference in distribution frequency between active and quiescent state of TA at-137G/C and-607C/A positions, respectively.ConclusionsIL-18gene promoter region-137G/C and-607C/A gene polymorphisms were associated with the pathogenesis of TA in Chinese Han population. However, thay had no relationships with the state (active and quiescent) of TA. IL-18gene promoter region-137G/C gene polymorphism may increase the risk of TA, and thus was a risk factor; while-607C/A may decrease the risk of TA, and thus was a protective factor. These findings may contribute to further studies of the correlation of IL-18gene polymorphism and TA. BackgroundPrevious studies suggest that inflammation is associated with development and prognosis of aortic dissection (AD). Inflammation could destroy the media layer of the aortic wall and eventually lead to dilation, dissection and rupture of the aortic wall. In the meanwhile, AD is a severe disease with high mortality. Therefore, early diagnosis and treatment are extremely essential. Biochemical diagnosis of AD is attractive in diagnosing and predicting the prognosis of AD because it is rapid and relatively easy to perform. However, those studies about the relationships between inflammatory biomarkers and AD have been limited by either small sample size or lack of systemic investigation.ObjectiveIn this study we evaluated the relationships between plasma levels of interleukin-6(IL-6), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9(MMP-9) and AD, and tried to confirm the clinical implication of these biomarkers in AD.MethodsThe plasma levels of IL-6, TNF-a, MMP-9and CRP in64patients with acute AD,42chronic AD,98patients with hypertension alone, and96healthy subjects were measured immediately on admission using ELISA and immunoturbidimetry, and compared among the four groups.ResultsIL-6concentrations were higher in acute AD than that in hypertension and healthy controls (10.98±2.38vs.3.79±1.56and3.32±1.60pg/ml, P<0.05, respectively). Increased CRP concentrations were found in acute AD compared with chronic AD and hypertension as well as healthy subjects (13.48±3.74vs.4.12±2.99,1.62±0.65and 1.12±0.35mg/1, P<0.001,respectively). Higher MMP-9concentrations were detected in acute AD, chronic AD and hypertension compared with healthy controls (37.75±9.38,55.78±6.41and31.03±7.94vs.21.24±7.28ng/ml, P<0.05, P<0.001and P<0.05, respectively), and in the dead compared to the survived (57.59±4.37vs.36.07±7.58ng/ml, P<0.001) among acute AD patients. Moreover, plasma MMP-9levels showed the highest levels in chronic AD compared with the other three groups (P<0.001). In acute AD, the time after onset had positive correlation with TNF-a (r=0.497, P=0.000), and negative correlation with CRP (r=-0.424, P=0.000). Moreover, we found positive correlation between CRP and the period of hospitalization (r=0.342, P=0.006, n=64). Plasma CRP levels showed significant difference among the three time period (0-12h,12-24h,24-48h)(P=0.013).ConclusionsOur findings confirmed and extended previous studies that increased plasma inflammatory markers were significantly associated with AD, and different markers had different clinical significance. BackgroundActivated coagulation and fibrinolytic systems are found in the pathogenesis of aortic dissection (AD). In AD, the ingredients of the aorta are injured resulting in the releasing of tissue factor into blood flow. This leads to the activation of extrinsic pathway of the coagulation cascade. Subsequently, fibrinolytic systems are also activated, cross-linked fibrin is degraded. D-dimer, a kind of degradation product of cross-linked fibrin, indicating fibrinolytic activities in AD, could be detected in peripheral blood. AD is a severe cardiovascular disease with high mortality. It has the characteristics of acute onset and rapid progress. A large number of studies have indicated the value of D-dimer in early diagnosis in AD. However, there is still lacking of systematic research about the role of D-dimer in predicting short-term death in acute AD. ObjectiveThe aim of this study was to assess the plasma D-dimer levels in patients with acute AD and evaluate the role of D-dimer in predicting hospital short-term death risk in acute AD, and thus further guide the treatment of acute AD.MethodsThis study enrolled114patients with acute AD, including83patients survived (survival group) and31patients died (death group) during hospitalization. The admission D-dimer concentrations were assayed by immunoturbidimetric method. The sensitivity and specificity of D-dimer in predicting short-term death risk in acute AD were investigated.ResultsAmong the114patients with acute AD,83patients survived and31died during hospitalization. Increased levels of plasma D-dimer (14.08±2.81vs.11.18±1.85mg/L, P=0.000), C-reactive protein (CRP)(14.08±2.81vs.11.18±1.85mg/L, P=0.000), and aortic diameter (45.2±9.5vs.40.3±6.0mm, P=0.007) were showed in patients died with acute AD comparing with those in patients survived. Moreover, plasma D-dimer concentrations in type A AD were higher that that in type B AD (6.51±4.11vs.4.87±2.29μg/ml, P=0.013). Correlation analysis showed that plasma D-dimer concentrations had positive correlations with CRP levels (r=0.527, P=0.000) and aortic diameter (r=0.227, P=0.015), while had negative correlations with the type of AD (r=-0.264, P=0.005) and the time from onset of symptoms to hospital admission (r=-0.264, P=0.005). Univariate analysis demonstrated that the type of AD, history of smoking, admission systolic blood pressure, admission diastolic blood pressure, aortic diameter, the time after onset of symptoms, were associated with hospital mortality. While the type of AD, D-dimer and CRP levels were strongly associated with hospital mortality in binary logistic regression analysis. The odds ratio (OR) and95%confidence interval (CI) were3.272,1.638-6.535(P=0.001);2.322,1.134-4.757(P=0.021);0.126,0.019-0.853(P=0.034), respectively. They were important risk factors for hospital short-term mortality in acute AD. Receiver operating characteristic curve showed that when the plasma D-dimer levels≥5.67μg/ml, the sensitivity and specificity of D-dimer in predicting short-term death risk in acute AD were90.3%and75.9%, respectively. The95%CI was0.85-0.96(P<0.001). Moreover, when plasma CRP levels≥11.21mg/L, the sensitivity and specificity were100%and54.2%, respectively. The95%CI was0.74-0.89(P<0.001).ConclusionsD-dimer≥5.67μg/ml, CRP≥12.05mg/L, and type A acute AD were important risk factors for acute AD hospital short-term death. These findings laid the basis for the further studies about predicting prognosis of acute AD. However, further study enrolling larger cohort, prospective study would be warranted.