Serum Metabolic Profiling Research Of Coronary Heart Disease Based On UPLC-MS

Objectives In this study, we use the metabolomics platform of UPLC-MS (ultra performance liquid chromatography-mass spectrometry) to analysis serum samples of patients with different pathological stages of CHD(coronary heart disease), respectively metabolomics analysis, to establish a disease distinguishing model and to select characteristic metabolites with potential clinical diagnostic value. We select the group of metabolic markers, which can effectively predict vulnerable plaque rupture, and filter out specific metabolic markers group, which can predict the prognosis of patients who have heartstroke and AMI (acute myocardial infarction). We verified these metabolic markers by observing the dynamic changes of serum samples during different time periods of patients who have AMI. We analysis these markers, research development in the pathogenesis of CHD and find new cure target.Methods UPLC-MS platform was used to analyze28health volunteers,17patients without coronary plaque, plaque group of27patients,17patients improved acute myocardial infarction,14cases of myocardial infarction death group. The data was pretreated and normalized by Mzmine2.0. Through PCA (principal component analysis) and OPLS-DA (orthogonal partial least squares discriminant analysis) of SIMCA-P+12.0.1.0, the disease distinguishing model was established. After that, the VIP (variable importance in projection) values, variable confidence intervals in the VIP plot and coefficient plot and non parameter test were used to select feature ions which can separate health volunteers, patients without coronary plaque, plaque group, patients improved acute myocardial infarction and myocardial infarction death group in the two-class OPLS-DA models, and these ions were then identified and assigned to corresponding metabolite. Then SPSS17.0was used for statistical analysis, at the same time, ROC curve was used to evaluate the clinical diagnostic performance of characteristic metabolites.Results This research successfully build a "Normal-Nor-aps-Aps-AMI(1-4)-Dead" of the principal component analysis (R2X=40.2%, Q2=40.2%) and orthogonal partial least-squares metabolic profile analysis model (R2X=79%, R2Y=79%, Q2=65%), and verify the results of model prediction accuracy reached100%. This research screen10characteristic ions which can help clinical doctors to predict the prognosis of patients with AMI and3characteristic ions which can not only predict the prognosis of patients with AMI but also predict the rupture of vulnerable plaques. These identified ions were mainly involved in phospholipid metabolic pathway. We creen and identify10kinds of ions that can estimate the prognosis of AMI.4-Hydroxy-6-docosanone,N-Acetyl-leukotriene E4, LysoPC(18:2(9Z,12Z)), LysoPC(18:0), LysoPC(P-16:0), LysoPC(P-18:1(9Z)), LysoPC(20:1(11Z)), LysoPC (20:2(11Z,14Z)) decrease in dead group, L-Threonine,3-Methyl-2-butene-l-thiol increase in dead group; L-Threonine,3-Methyl-2-butene-l-thiol and4-Hydroxy-6-docosanone metabolic ions not only can predict the prognosis of patients with AMI but also have high diagnostic value to the diagnosis of AMI; L-Threonine,3-Methyl-2-butene-l-thiol, N-Acetyl-leukotriene E4and4-Hydroxy-6-docosanone may be the new therapeutic targets of AMI; From nor-aps, aps to AMI, the level of hemolysis phosphatidyl choline decrease, and during the treatment of the dynamic monitoring we confirme that in the early period of AMI the level of hemolysis phosphatidyl choline increase and can be corrected, after that the level decrease and can not be corrected; LysoPC(18:0), LysoPC(P-18:1(9Z)) and m/z=341.304metabolic ions have high diagnostic value to angina pectoris.Conclusions The specific metabolic markers group we find can effectively predict vulnerable plaque rupture and predict the prognosis of patients who have AMI. These ions are considered to be potential diagnostic biomarkers and benefit in further clinical study as novel drug targets. And, after analysis of the identified metabolites, we find that L-Threonine,3-Methyl-2-butene-l-thiol and4-Hydroxy-6-docosanone in serum with UPLC-MS become more effective means of monitoring and evaluation of myocardial infarction. We also find that L-Threonine,3-Methyl-2-butene-1thiol, N-Acetyl-leukotriene E4and4-Hydroxy-6-docosanone may become the new target for treatment of AMI; LysoPC(18:0).LysoPC(P-18:1(9Z)) and m/z=341.304ions have high diagnostic value to angina pectoris.