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Study On LncRNA-TUG1/miRNA-132,IL-1β And IL-18 In Plasma Of Patients With Acute Coronary Syndrome

Posted on:2022-12-02Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y WangFull Text:PDF
GTID:2504306761956799Subject:Emergency Medicine
Abstract/Summary:PDF Full Text Request
Background:In clinical practice,acute coronary syndrome(ACS)is a prevalent acute myocardial ischemia syndrome.It includes acute myocardial infarction(AMI)and unstable angina pectoris(UA).One of the most common causes of cardiovascular death is ACS.Its early detection and treatment are critical.Pyroptosis is currently being researched as a novel type of cell death.It’s worth debating if pyroptosis-related parameters can be employed as ACS diagnostic indicators.Pyroptosis is a form of cell death that occurs in conjunction with an inflammatory response.It has recently been discovered to be linked to ACS.Its signature inflammatory factors,IL-1β and IL-18,are cleaved by caspase-1 and released into the extracellular space via the endothelial cell membrane’s gastermin-d(GSDMD),which attracts more inflammatory cells and expands the inflammatory response,leading to endothelial cell death and accelerated plaque formation.Noncoding RNAs(nc RNAs)have been discovered to play a significant role in cardiovascular disease.In different pathological cases,its expression will change.As a result,it can be used as a non-invasive diagnostic tool.One of the lnc RNAs is taurine upregulated gene 1(TUG1),a long noncoding RNA.TUG1 was found to be linked to cardiomyocyte pyroptosis in in vitro tests.By suppressing miR-186-5p and then targeting XIAP,overexpression of TUG1 can attenuate lipopolysaccharide-induced cardiomyocyte pyroptosis.TUG1 generated by ischemia-reperfusion absorbs miR-132-3p through the sponge,activates histone deacetylase 3,targets several protective genes,induces intracellular ROS buildup,and aggravates AMI damage in mouse cardiomyocytes.By targeting SIRT1,miR-132 was discovered to increase oxidative stress-induced pyroptosis in cardiac ischemia-reperfusion damage.Whether plasma TUG1 and miR-132 are involved in pyroptosis generated by acute coronary syndrome,whether TUG1 governs the development of acute coronary syndrome by regulating miR-132,and their predictive value for myocardial infarction are still unknown.Objective:The expression variations of pyroptosis-related TUG1 and miR-132,IL-18,and IL-1β in plasma in the acute coronary syndrome group and the control group were detected in this investigation,and the differences between the groups were compared,as well as the four detection indices.The value of the four in the identification of acute coronary syndrome,as well as the link with the severity of coronary artery disease.Methods:From May to November 2021,a total of 75 patients admitted to affiliated hospital of Jilin University were diagnosed with ACS for the first time,including 40 patients in the AMI group and 35 patients in the UA group.In the control group,26 patients were admitted to the hospital at the same time and had coronary angiography or coronary CT examination.There was no evidence of severe coronary artery stenosis.Trans Zol Up was used to extract total RNA from plasma,and q RT-PCR was used to detect TUG1 and miR-132 expression.By using an enzyme-linked immunosorbent assay(ELISA),the amounts of IL-18 and IL-1β in the two groups were measured.Spearman was used to analyze the correlation among the four patients and the correlation between IL-18,IL-1β and Gensini score.The prediction of plasma TUG1,miR-132,IL-18,and IL-1βfor acute coronary syndrome was evaluated using a receiver operating characteristic curve(ROC).Results:(1)There were no significant differences in age,gender,diabetes,hypertension,history of drinking,TG,TC,LDL-C,lipoprotein a,uric acid,BMI,and creatinine between the two groups(p > 0.05);however,the ACS group’s smoking history was higher than the control group’s(p< 0.05),and the ACS group’s white blood cell count and neutrophil count were higher than the control group’s(p< 0.05).(2)TUG1,miR-132,IL-18,and IL-1β were examined in the control and ACS groups.TUG1(p< 0.01),IL-18(p< 0.01),and IL-1β(p< 0.01)expressions were higher in the ACS group than in the control group,but miR-132 expression was lower(p<0.01).(3)The effects of TUG1,miR-132,IL-18,and IL-1β in the ACS subgroup and control group were investigated further.Plasma TUG1 expression was higher in the AMI group than in the UA group(p<0.01)or the Control group(p<0.01),but there was no significant difference between the UA and Control groups(p>0.05).The plasma miR-132 expression in the UA group was significantly lower than that in the Control group(p<0.01),and the expression of 132 in the UA group was significantly lower than that in the Control group(p<0.01).The expression of plasma IL-1β in the AMI group was higher than that in the UA group(p<0.01)and Control group(p<0.01),but there was no significant difference between the UA group and the Control group(p> 0.05).AMI group had higher plasma IL-18 expression than UA group(P <0.01)and Control group(p<0.01),respectively,and UA group had higher plasma IL-18 expression than Control group(p<0.05).(4)The correlation between the four indicators was investigated using Spearman correlation analysis.TUG1 was shown to be negatively linked with miR-132(r=-0.434,p<0.05)in the study.TUG1 was found to be positively linked with both IL-1β(r=0.301,P<0.05)and IL-18(r=0.292,p<0.05).miR-132 had no significant relationship with IL-1β(r=-0.196,p > 0.05)or IL-18(r=-0.179,p > 0.05).(5)IL-1β and IL-18,as well as Gensini scores,were analyzed for correlation.The expression of IL-1β was found to have a positive relationship with the Gensini score(r=0.299,p<0.05).The expression of IL-18 was shown to be favorably linked with the Gensini score(r=0.240,p<0.05).(6)The AUC of TUG1 expression in plasma for the diagnosis of ACS was 0.836(95% CI: 0.759-0.914,p<0.01),with 61.3% sensitivity and 96.2% specificity,respectively;the AUC of miR-132 expression in the diagnosis of ACS was 0.957(95%CI: 0.920-0.995,p<0.01),with 89.3% sensitivity and 96.2% specificity,respectively;The AUC of IL-1β expression in plasma for the diagnosis of ACS was 0.764(95% CI:0.653-0.875,p<0.01),with 86.7 % sensitivity and 57.7% specificity,respectively;the AUC of IL-18 expression in plasma for the diagnosis of ACS was 0.843(95% CI:0.736-0.950,p<0.01),with 93.3 % sensitivity and 65.4% specificity,respectively.Further subgroup analysis revealed that the AUC of TUG1 expression in plasma for the diagnosis of AMI was 0.934(95% CI: 0.883-0.984,p<0.01),with a sensitivity and specificity of 87.5% and 90.2%,respectively;miR-132 expression in plasma for AMI diagnosis was 0.832(95% CI: 0.754-0.910,p<0.01),with 75.0% sensitivity and 80.3%specificity,respectively;for the diagnosis of AMI,the AUC of IL-1β expression in plasma was 0.791(95% CI: 0.705-0.877,p<0.01),with 75.0% sensitivity and 68.9%specificity,the AUC of IL-18 expression in plasma was 0.835(95% CI: 0.755-0.915,p<0.01),with 75.0% sensitivity and 83.6% specificity,respectively.The expression levels of plasma miR-132 and IL-18 in the UA and Control groups were used to create ROC curves.The AUC of plasma miR-132 expression for the diagnosis of UA was0.926(95% CI: 0.861-0.992,p<0.01).The sensitivity and specificity were 82.9% and96.2%,respectively;for the diagnosis of UA,the AUC of IL-18 expression in plasma was 0.794(95 percent CI: 0.668-0.920,p<0.01),with a sensitivity and specificity of100.0% and 57.7%,respectively.Conclusions:1.In patients with ACS,the expression of pyroptosis related TUG1,IL-1β and IL-18 was significantly increased,while the expression of miR-132 was significantly decreased.TUG1 expression was negatively correlated with miR-132,and TUG1 expression was positively correlated with IL-18 and IL-1β,but miR-132 expression was not significantly correlated with IL-18 and IL-1β.2.In the ACS group,IL-1β,and IL-18 demonstrated some prognostic value for the severity of coronary artery lesions.3.TUG1,miR-132,IL-1β and IL-18 could be used to aid in the diagnosis of AMI,and miR-132 and IL-18 could be used to aid in the diagnosis of UA.
Keywords/Search Tags:Acute coronary syndrome, Non-coding RNA, Interleukin, Gensini score, pyroptosis
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