Study On The Changes Of Serum Metabolites In Patients With Acute Ischemic Stroke And Its Different Subtypes

Background:Stroke is one of the main causes of human death and disability and is associated with a high rate of disability and recurrence.According to population-based studies,ischemic stroke(IS)accounts for more than 80%of all strokes.According to its etiology and imaging,IS can be categorized into five subtypes,including large artery atherosclerosis(LAA),small artery occlusion(SAO),cardioembolism,stroke of other determined cause,and stroke of undetermined cause.The classification of IS can help with the early treatment and prevention of long-term recurrence in patients.However,the diagnosis and classification of IS mainly rely on neuroimaging techniques,which are scarce,expensive,and time-consuming.It is difficult to release macromolecules from the brain into the blood due to the presence of the blood-brain barrier.Some conventional detection methods make it difficult to detect specific sensitive different metabolites in patients with IS.However,with the development of the emerging science of metabolomics,it may be possible to identify specific small molecular biomarkers in patients with IS and determine the underlying etiology.Metabolomics is an effective method to reveal biomolecules’ phenotypes.This method enables the identification of changes in small molecular metabolites in various diseases,which can greatly help in understanding and diagnosing diseases.Many studies using metabolomics have revealed the differences in metabolites between patients with acute ischemic stroke(AIS)and healthy controls.To date,few studies have few studies have explored the differences in metabolites between the LAA and SAO subtypes of IS.Objective:This study aims to explore the serum significantly changed metabolites and related different metabolic pathways between IS patients and healthy individuals and between LAA and SAO groups which classified by TOAST,and find potential clinical biomarkers for clinicians to promote the secondary prevention and treatment of IS patients.Methods:Enrolled 100 AIS patients from the ischemic cerebrovascular disease database and blood database of The First Affiliated Hospital of Zhengzhou University,including 50 patients with LAA and 50 patients with SAO.And a total of 50 HCs with age,sex,and risk factors matched with the AIS group were recruited.A comprehensive metabolic profile analysis method based on LC-MS was used to detect serum significantly changed metabolites,identify compounds that are likely to have statistically significant changes in their abundances within each group,and generate an information list of relevant characteristic peaks.Unsupervised principal component analysis(PCA),supervised orthogonal projections to latent structures-discriminant analysis(OPLSDA),single variance analysis and T-test statistics methods were used to analyze the difference metabolites between groups.Using Variable Importance in the Projection(VIP>1)and combined with T-test P value(P<0.05)in the OPLS-DA model to find significantly changed metabolites.Differential metabolic pathways between groups were analyzed according to the significantly changed metabolites.Results:1.There were 18 significantly different metabolites,such as oleic acid,linoleic acid,arachidonic acid,L-glutamine,L-arginine,and L-proline,between patients with AIS and HCs.These different metabolites are closely related to many metabolic pathways,such as fatty acid metabolism and amino acid metabolism.2.There were also differences in metabolic profiling between the LAA and SAO groups.There were eight different metabolites,including L-pipecolic acid,1Methylhistidine,PE,LysoPE,and LysoPC,which affected glycerophospholipid metabolism,glycosylphosphatidylinositol-anchor biosynthesis,histidine metabolism,and lysine degradation.Conclusions:Our study effectively identified the metabolic profiles of IS and its subtypes.The different metabolites between LAA and SAO may be potential biomarkers in the context of clinical diagnosis.These results highlight the potential of metabolomics to reveal new pathways for IS subtypes and provide a new avenue to explore the pathophysiological mechanisms underlying IS and its subtypes.