Expression Of Serum Inflammation Related MicroRNA And Clinical Significance In Carotid Atherosclerosis

Objective:By observing the differences in expression of five kinds of inflammation-related microRNAs and three kinds of inflammatory cytokines in the peripheral blood serum of patients with carotid atherosclerosis stenosis and normal carotid arteries,and to explore the relationships in carotid atherosclerosis stenosis,microRNA,inflammatory cytokines and plaque vulnerability,In order to find biomarkers that can detect carotid atherosclerotic stenosis early and predict the vulnerability of carotid atherosclerotic plaque.Methods:According to Doppler ultrasound examination,a total of 180 patients with carotid intima-media thickening or carotid atherosclerotic plaque formation,were as carotid atherosclerotic stenosis group(stenosis group),and according to the stenosis classification,the stenosis group was divided into three subgroups:mild stenosis group(64 cases),moderate stenosis group(62cases),severe stenosis group(54 cases).besides,according to the characteristic of atherosclerotic plaque,the stenosis group was divided into stable plaque group(78 cases)and vulnerable plaque group(84 cases).While a total of 90 people without carotid atherosclerosis as normal group.All enrolled patients were collected fasting peripheral venous blood in the morning.Separated the serum and extracted RNA.Then the expression of microRNA-21,microRNA-126,microRNA-146 a and microRNA-125 b in peripheral blood serum of each group were determined by Real-time qPCR.The levels of inflammatory cytokines IL-6,CRP and TNF-? in peripheral blood serum were determined by Enzyme-linked immunosorbent assay(ELISA).Logistic regression analysis was used to analyze the risk factors of carotid atherosclerosis.Spearman correlation analysis was used to analyze the relationship of five serum micro RNAs,carotid artery stenosis,three inflammatory cytokines and carotid plaque vulnerability.ROC Curves to evaluate the value of five microRNAs in predicting carotid atherosclerotic plaque vulnerability.Results:1.There was no significant difference in the general data between the stenosis group and the normal group(P>0.05).The Logistic regression analysis showed that hypertension and high LDL-C level were the risk factors for the development of carotid atherosclerosis,while high HDL level was a protective factor.2.The expression levels of serum microRNA-21,microRNA-210,and microRNA-146 a in the stenosis group were significantly higher than the normal group,and the degree of atherosclerosis stenosis was positively correlated with the level of the four serum microRNA(P<0.05).The expression of micro RNA-125 b in the stenosis group was lower than the normal group,but the expression level of microRNA-125 b was not correlated with the degree of carotid atherosclerosis(P>0.05).3.(1)The levels of serum microRNA-21,microRNA-210,micro RNA-126 and microRNA-146 a in stable plaque group were lower than the vulnerable plaque group(P<0.05),while microRNA-125 b expression was higher than vulnerable plaque group(P<0.05)(2)Correlation analysis showed that serum microRNA-21,microRNA-210,microRNA-126,and microRNA-146 a expression was positively correlated with the vulnerability of carotid atherosclerosis plaques(P<0.05).While the expression level of micro RNA-125 b in stenosis group was no correlation with the vulnerability of plaque(P>0.05).(3)ROC curves showed that the AUC,witch the area under the curve of microRNA-21,microRNA-210,micro RNA-126,microRNA-146 a expression to predict carotid atherosclerotic plaque vulnerability,were 0.713,0.842,0.803,0.641(P<0.05).While microRNA-125 b was no predictive value(P>0.05).4.(1)The levels of three kinds of serum inflammatory cytokines in stenosis group were higher than the normal group(P<0.05).(2)The levels of IL-6,TNF-? and CRP in the severe stenosis group were significantly higher than the mild and moderate stenosis group(P<0.05).The expression levels of IL-6 and TNF-? in moderate stenosis group was significantly higher than the mild stenosisgroup(P<0.05).However,there was no significant difference in CRP expression between the mild and the moderate stenosis group(P>0.05).The expression levels of IL-6 and TNF-? in the stable plaque group was significantly lower than the vulnerable plaque group(P<0.05),While there was no difference in CRP expression between the stable plaque group and the vulnerable plaque group(P>0.05).(4)The expression levels of IL-6 and TNF-? in the stenosis group were positively correlated with the vulnerability of carotid atherosclerotic plaques(P<0.05).However,There was no correlation between the CRP expression and the vulnerability of the plaque(P>0.05).5.(1)The expression of microRNA-21,microRNA-210 and micro RNA-146 a in stenosis group was positively correlated with the level of IL-6 and CRP,while no correlation found between the expression of microRNA-125 b,microRNA-126 and the level of IL-6,CRP(P>0.05).(2)The expression of microRNA-21,microRNA-210,microRNA-126,microRNA-146 a microRNA-146 a in the stenosis group were positively correlated with TNF-?(P<0.05),while there was no correlation between the expression of microRNA-125 b and TNF-?.Conclusions:1.Hypertension,high LDL-C levels are risk factors for carotid atherosclerotic stenosis,and high HDL-C levels are protective factors for carotid atherosclerotic stenosis.2.micro RNA-21,microRNA-210,microRNA-126 and microRNA-146 a have a positive correlation with the degree of carotid atherosclerosis.These four microRNAs can be used as an indicator of the degree of carotid atherosclerosis.And the serum levels of microRNA-21,microRN A-210,microRNA-126 and micro RNA-146 a have excellent predictive value for the vulnerability of carotid artery atherosclerotic plaque.And the serum levels of microRNA-210 for predicting the vulnerability of carotid artery atherosclerotic plaque is the best.3.Increased expression of inflammatory cytokines IL-6 and TNF-? is closely related to the occurrence,development and vulnerability of carotid atherosclerosis.4.microRNA-21,microRNA-210,microRNA-146 a and microRNA-126 could not only through regulating theexpression of TNF-? to participate in the occurrence and development of carotid atherosclerosis,and microRNA-21,microRNA-210,microRNA-146 a could regulate the expression of IL-6,CRP by involved in the occurrence and development of carotid atherosclerosis.