Expression And Clinical Significance Of LncRNA000440 In Peripheral Blood Monocytes Of Patients With Coronary Artery Disease

Research background and objective:Coronary artery disease(CAD)has a serious impact on human health and the mortality is growing increasely in our country,although great progress has been made in percutaneous coronary intervention.Therefore,it is urgent to identify and prevent CAD in the early stage.Long non-coding RNA(lncRNA)is a transcript with a length of at least 200 nucleotides,which regulates a variety of biological processes.Many researches indicated that lncRNA plays a critical role in the pathogenesis of CAD.In recent years,a large number of studies on the molecular mechanism of lncRNA and CAD have emerged,but the clinical research is still in the preliminary stage,and there are still a large number of lncRNA has not been discovered.In addition,inflammation throughout the pathogenesis of CAD.Imterleukin-1 β(IL-1 β),interleukin-6(IL-6)and tumor necrosis factor α(TNF-α)are pro-inflammatory factors secreted by monocyte macrophages.Besides,their abnormal expressions are associated with atherosclerotic plaque formation and plaque instability.Some studies have shown that lncRNA can interact with inflammatory factors.Through sequencing study,our team found a lncRNA,namely long non-coding RNA000440(lncRNA000440)and further research showed that the expression of lncRNA000440 in THP-1 monocytes / macrophages induced by ox-LDL was markly increased compared with control,which indicated it might be relevant to the occurrence and development of atherosclerosis.However,the expression level of lncRNA in clinical patients with coronary artery disease and the relationship with inflammation is not clear,and the relevant clinical application value still needs to be explored.Thus,our study aim to explore the clinical application value of lncRNA000440,understand the relationship between lncRNA000440 and inflammation and further to provide some ideas for the diagnosis and treatment of CAD,especially for the early evaluation of acute coronary syndrome mainly by measuring the relative expression of lncRNA000440 in peripheral blood monocytes of patients with different types of CAD,and analyzing its correlation IL-1β,IL-6 and TNF-α and the correlation between the lncRNA and Gensini score and global acute coronary event registered risk score.Methods:A total of 110 patients who were hospitalized in the Department of Cardiology,the Second Hospital of Dalian Medical University from July 2020 to December 2020 because of chest pain and chest tightness were selected including 30 cases in the control group and 80 cases in the coronary artery disease group whose baseline conditions such as sex and age were similar compared with control group.The coronary artery disease group was further divided into two subgroups: SCAD group and NSTEACS group.All selected patients were asked about their medical history by cardiologists and underwent coronary angiography or coronary CT examination.The clinical baseline data of all subjects were recorded and three inflammatory indexes were statistically analyzed.The Gensini scores of all selected patients with coronary artery disease were calculated,and evaluated the GRACE scores with acute coronary syndrome.The expression level of lncRNA000440 in peripheral blood mononcyte in different groups of patients were measured by q RT-PCR method.SPSS26.0 and Graph Pad Prism 7.0 analyze statistical data,P<0.05(bilateral)indicates the difference was statistically significant.Results:1.Analysis of the expression of lncRNA000440 in peripheral blood monocytes of patients with different types of coronary artery disease: compared with healthy controls,the expression level of lncRNA000440 in peripheral blood monocytes in coronary artery disease group was lower than that in healthy controls(P < 0.05).The expression level of lnc000440 in NSTEACS group was significantly lower than that in control group and SCAD group(P < 0.001),but there was no significant difference between SCAD group and control group by ananlyzing the difference of lncRNA000440 expression among control group,SCAD group and NSTEACS group.And there was no significant difference between UA group and NSTEMI group by further analysis of the expression level of lncRNA000440 between them.2.The correlation between the relative expression of lncRNA000440 and related clinical features: the relative expression of lncRNA000440 was positively correlated with age,absolute value of monocytes and blood glucose level,and the difference was statistically significant(P < 0.05).3.Analysis of the correlation between the relative expression of lncRNA000440 and inflammatory indexes: the results showed that the relative expression of lncRNA000440 in CAD group was negatively correlated with TNF-α(R=-0.570),but there was no significant difference between IL-1β and IL-6.4.Analysis of the correlation between the relative expression of lncRNA000440 and GRACE score and Gensini score: the relative expression of lncRNA000440 in CAD group was negatively correlated with GRACE score(R=-0.279).But,there was no significant difference in the expression level of lncRNA000440 among the three groups when the patients in NSTEACS group were divided into low,medium and high risk groups according to the GRACE score.Besides,there was no significant difference in correlation analysis between the relative expression of lncRNA and Gensini score.Conclusions:1.The expression level of lncRNA000440 minght be helpful for the diagnosis of coronary artery disease,especially for NSTEACS.2.The expression level of lncRNA000440 might have critical clinical significance for evaluation of NSTEACS.