Plaque And Circulatory Markers In The Culprit Of Acute Myocardial Infarction

Background:Plaque rupture,plaque erosion and calcified nodule are the three pathological types in patients with acute myocardial infarction.At present,intravascular optical coherence tomography is often used to distinguish the types of plaque in patients,but other biomarkers are lacking.Previous reports have shown that miRNAs are largely involved in the regulation of the pathophysiological mechanisms of plaque rupture and plaque erosion.Considering that OCT is expensive and difficult to promote,this study analyzed the differential expression of plasma miRNAs in ST-segment elevation myocardial infarction(STEMI)patients with plaque rupture and erosion to search circulating miRNA markers with diagnostic value for distinguishing two types of plaques.Methods:In this study,21 STEMI patients with plaque rupture,20 STEMI patients with plaque erosion and 17 healthy controls were selected.Plasma of the patients was collected and miRNAs were extracted.All the population were detected by miRNA sequencing.According to the sequencing results of differentially expressed miRNAs,we establish the validation cohort of 20 patients with plaque rupture and 20 patients with plaque erosion and total RNA in the patient's plasma was extracted.Quantitative real-time polymerase chain reaction(qPCR)was used to determine the level of differentially expressed miRNAs.Finally,a large sample replication cohort of 82 patients with plaque rupture,84 patients with plaque erosion,and 59 healthy controls was set up to further verify the above-mentioned differentially expressed miRNAs.Results:In all 58 samples of miRNA sequencing,1305 mature and known miRNA were detected,and the p value of each miRNA is corrected by multiple testing to obtain the Q value.After selection.80 miRNAs were up-regulated and 117 miRNAs were down-regulated compared with patients with plaque erosion.According to the expression level of miRNA in the sequencing sample,a receiver operating characteristic curve(ROC)to distinguish between plaque rupture and erosion is made,and miRNAs with an area under the curve(AUC)>0.6 are selected.Moreover,we referred to previous study to select 24 miRNAs that may be related to the mechanism of plaque rupture.The expressions of miR-744-3p,miR-641,miR-4435,miR-330-3p,miR-324-3p,miR-495-3p,miR-6772-3p in the validation cohort have significant differences between plaque rupture and erosion.The replication cohort results showed that the expression of miR-744-3p,miR-324-3p and miR-330-3p was not only significantly higher in plaque rupture than in plaque erosion,but also significantly higher in patients with STEMI than the normal.The 166 patients in the replication cohort were randomly divided into 115 people in the training set and 51 people in the validation set according to 7:3.ROC analysis showed that combination of circulating miR-744-3p,miR-324-3p and miR-330-3p could distinguish between plaque rupture and plaque erosion.The AUC in the test set was 0.764 and in the validation set was 0.768.Conclusion:Circulating miRNAs are differentially expressed in STEMI patients with plaque rupture and plaque erosion.Among them,combination of circulating miR-744-3p,miR-324-3p and miR-330-3p can predict STEMI patients with plaque rupture,and provide a basis for risk stratification and precise treatment of STEMI patients.Background:Hyaluronan(HA)is the main component of extracellular matrix,which plays an important role in regulating tissue damage and repair and affecting the prognosis of diseases.The metabolism of HA is extensively known to be involved in the pathophysiological process of acute coronary syndrome,but it is unclear how circulating HA levels change in ST-Segment-Elevation Myocardial Infarction(STEMI)patients and whether HA is related to plaque morphology,including plaque rupture and plaque erosion.This study concentrated in the changes of the plasma levels of high molecular weight(HMW)HA and CD44 in STEMI patients and their association with plaque morphology evaluated by optical coherence tomography(OCT).Methods:We prospectively enrolled 3 cohorts in this study,including 162 patients with STEMI,34 patients with stable coronary artery disease(SCAD)and 50 healthy controls.Plaque morphology was detected by OCT analysis,and the plasma levels of HMW HA and CD44 were examined by enzyme-linked immunosorbent assay(ELISA).We compared plasma level of HMW HA and CD44 among STEMI patients,SCAD patients and healthy controls,as well as in plaque rupture and plaque erosion.Results:The plasma levels of HMW HA and CD44 were significantly lower in STEMI patients than in healthy controls(30.1ng/ml(17.6-47.7)vs.39.3ng/ml(26.0-53.7)p=0.009;143.7ng/ml(126.2-162.8)vs.178.7ng/ml(160.1-191.3)p<0.001,respectively).In addition,plasma level of HMW HA in plaque erosion was significantly lower than that in plaque rupture(25.1ng/ml(15.4-41.4)vs.36.2ng/ml(18.9-51.9)p=0.021),whereas no differences were found in plasma level of soluble CD44 between plaque rupture and erosion.Conclusions:Low levels of plasma HMW HA and CD44 were independently correlated with STEMI,and low levels of HMW HA were associated with plaque erosion compared with rupture.Moreover,plasma HMW HA might be a useful biomarker for identifying plaque erosion to improve the risk stratification and precise management of STEMI patients.Background:Healed plaque indicates recurrent regional plaque rupture or erosion.Trimethylamine N-oxide(TMAO)is related to plaque burden,vulnerability and risk of cardiovascular events.In this study,we investigated the association of plasma level of TMAO and healed culprit plaque in ST-segment elevation myocardial infarction(STEMI)patients.Methods:Herein,206 STEMI patients who were detected by optical coherence tomography(OCT)were analyzed in our study.After exclusion,156 patients were categorized into two groups:54 patients with healed plaque and 102 patients without healed plaque.Plasma TMAO levels of these patients were detected by stable isotope dilution liquid chromatography tandem mass spectrometry.Results:Patients with healed plaques had higher age and lower body mass index(BMI)than patients without healed plaques.Patients with healed plaque had more vulnerable features than those without healed plaque under OCT findings,such as plaque rupture(P<0.001)thin cap fibroatheroma(TCFA)(P=0.004)and macrophages(P<0.001).Moreover,plasma TMAO level in patients with healed plaque is significantly higher than patients without healed plaque.Additionally,healed plaque can be predicted by the plasma level of TMAO with a cutoff value of 2.97?M according to the receiver operating characteristic curve.The area under curve(AUC)was 0.810.Conclusions:Healed plaque in STEMI patients is associated with a high level of plaque vulnerability and inflammation.A high level of plasma TMAO can be a useful biomarker to differentiate STEMI patients with healed culprit plaques.Backgroud:The presence of calcified plaques is one of the pathological phenotypes of acute coronary syndrome(ACS)and can be frequently found in culprit lesion segments.Trimethylamine N-oxide(TMAO)is reported to be involved in vascular calcification and plaque instability.This study investigated the relationship between plasma TMAO levels and calcified lesions in culprit lesion segments in STEMI patients.Methods:A prospective series of 179 patients with STEMI were enrolled,and calcified lesions from 127 patients were analyzed by OCT.The plasma TMAO levels were measured and patients were divided into two groups according to the median plasma TMAO level.Results:The prevalence of calcified lesion,especially intimal calcified lesions in the high TMAO group was significantly higher than that in the low TMAO group(90.6 vs.57.1%,p<0.001;84.4 vs.44.4%,p<0.001).After adjustment of traditional risk factors and medication history,patients with calcification in their culprit lesion segments had higher plasma TMAO levels than those without calcification.Besides,plasma TMAO levels positively correlated to the parameters of calcium burden significantly,including maximal calcification arc(r=0.392,p<0.001),maximal calcification thickness(r=0.443,p<0.001),and calcified length(r=0.466,p<0.001).Conclusion:These results suggested that the level of TMAO is significantly correlated with the incidence of calcification in the culprit lesion segment,and the measurement of TMAO levels might help to identify the patients with heavy calcification.