Changes And Clinical Significance Of Plasma IL-22 And MMP-9 Levels In Patients With Chronic Atrial Fibrillation

Objective Atrial fibrillation(AF)is one of the most common tachyarrhythmias in clinic.Epidemiology shows that the total prevalence of AF increases year by year,and the age of onset is becoming younger.In addition,AF induced thromboembolism and hemodynamic changes can seriously endanger people's physical and mental health.Therefore,it is extremely important to explore its pathological mechanism and prevent it.Previous studies have shown that the inflammatory response caused by inflammatory cytokines is closely related to the occurrence and development of AF.Further studies have confirmed that some inflammatory cytokines can act on matrix metalloproteinase-9(MMP-9),and promote the formation of myocardial fibrosis and atrial structural remodeling,so that AF can occur and maintain.Interleukin-22(IL-22)is an inflammatory cytokine cloned from IL-9-treated mouse BW5147 T lymphoma cells.Previous studies have shown that IL-22 is not only related to inflammatory diseases,but also closely related to myocardial fibrosis induced by MMP-9.However,the role of IL-22 in the pathogenesis of AF is still unclear,the relationship between IL-22 and atrial structural remodeling needs further studies.Therefore,we have tested the levels of IL-22 and MMP-9 in the plasma of patients with chronic AF,in order to further explore their roles in AF and provide theoretical basis for better prevention and treatment of AF in clinical.Methods: 1.Subject selection According to the 2016 European AF management guidelines,113 patients were selected in our hospital from August 1,2018 to October 1,2019.In the AF group,there were 86 patients(53M/33 F,mean age 67.03±10.23 years).Among them,the paroxysmal atrial fibrillation(Pa AF)group had 30 patients(15M/15F;mean age 68.07±10.26 years);the persistent atrial fibrillation(Pe AF)group had 26 patients(14M/12 F,mean age 66.38±10.91 years);the permanent atrial fibrillation(Pe AF)group had 30 patients(24M/6F,mean age 66.57±9.84 years).In the sinus rhythm(SR)group,there were 27 patients(15M/12 F,mean age 62.85±8.00 years)who had no history of AF.Based on the spirit of the Declaration of Helsinki,all patients had been approved by the hospital's Ethics Committee,and we had obtained the informed consent of patients and their families in advance.All patients were recorded age,gender,BMI,past medical history,medication history,blood pressure,laboratory tests and radiation examinations etc.The patients were excluded who with valvular heart disease,cardiac function ?-?(NYHA),AMI,acute severe infection,malignant tumor,severe pulmonary fibrosis,autoimmune system disease,endocrine system disease,thromboembolic diseases(cerebral infarction,acute pulmonary embolism and lower extremity venous thrombosis),serious skin disease,etc.2.Experimental method Blood specimens were collected by venipuncture into a vacuum blood collection tube containing EDTA(3ml).The supernatant was obtained by centrifugation(15 min at 3000r/min).The plasma samples were stored at-80?.The plasma levels of IL-22 and MMP-9 were measured by ELISA.Using Philips IE33 cardiac color Doppler ultrasound system to test the patient's left atrial diameter(LAD),left ventricular(LV),left ventricular posterior wall(LVPW)and left ventricular ejection fraction(LVEF).3.Statistical method The statistical analyses were performed using SPSS 22.0.The enumeration data were expressed as percentage(%)and compared by Chi-square analysis.The measurement data were represented by mean±standard deviation (?) for normal distribution and by median+interquartile [M(QR)] for skew distribution,T-test or ANOVA were used to compare the data accorded with normal distribution and homogeneity of variance,otherwise Mann Whitney U test was used.The correlation analysis was undertaken with the linear correlation analysis.Logistic regression models were created to identify independent predictors of AF.The receiver operating characteristic curve(ROC)was used to evaluate the predictive power,and the area under the ROC curve(AUC)was used to estimate the sensitivity and specificity as well as the best cut-off value for the selected variable.P<0.05 was statistically significant.Result: 1.Compared with the SR group,the levels of IL-22 and MMP-9 in AF group were significantly increased,and LAD was significantly increased(P<0.05).2.Compared with the Pe AF group and the Pa AF group,the levels of IL-22 and MMP-9 in the Pm AF group were significantly increased(P<0.05),but there was no significant difference between the Pe AF group and the Pa AF group(P>0.05).3.Compared with the EHRA? group and the EHRA?group,the levels of IL-22 and MMP-9 in the EHRA? group were significantly increased(P<0.05).Compared with the EHRA? group,the levels of IL-22 and MMP-9 in the EHRA? group were significantly increased(P<0.05).4.There was a positive correlation between IL-22 and MMP-9 in plasma of patients with AF(r=0.568,P<0.05,Y=3.979+0.122X).There was a positive correlation between plasma MMP-9 level and LAD in AF group(r=0.228,P<0.05,Y=37.479+0.192X).5.Logistic regression analysis showed that IL-22(OR=1.021,95%CI=1.002-1.040),MMP-9(OR=1.164,95%CI=1.046-1.295),DD(OR=25.883,95%CI=1.296-516.893),FIB(OR=25.187,95%CI=4.007-158.302).6.The ROC analysis showed that the AUC of IL-22 was 0.707(95%CI=0.596-0.818),the optimal cut-off value was 128.31pg/ml(sensitivity: 93.0%;specificity: 37.0%).The AUC of MMP-9 was 0.774(95%CI=0.682-0.865),the optimal cut-off value was 25.43ng/ml(sensitivity: 57.0%;specificity: 88.9%).Conclusion: 1.IL-22 and MMP-9 are involved in the development and maintenance of AF.2.IL-22 and MMP-9 are indicators to determine the severity of AF.3.IL-22 and MMP-9 are independent risk factors for AF.4.IL-22 may participate in atrial remodeling of AF through MMP-9.