The Identification Of Lipid Biomarkers For Cardio-cerebral Vascular Diseases By LC-MS/MS

Nowadays cardio-cerebral vascular diseases?CVD?remain a leading cause of death.Finding reliable biomarkers associated with CVD is important for the diagnosis of this disease at early stage and can increase the efficacy of therapy.LC-MS/MS was widely used in metabonomics due to its excellent selectivity and sensitivity.In the present study,targeted quantification methods based on LC-MS/MS were established to find and confirm biomarkers of CVD,and to study the connection between lipid metabolites and CVD.1.Finding potential lipid biomarkers correlated to atherosclerosis progression using targeted lipidomics.Lysophospholipids?Lyso-PLs?were demonstrated to be closely related with the progression of atherosclerosis.At the present study,we investigated the influence of high-fat diet on Lyso-PL profiles of ApoE^-/-mice and their littermates to find the potential biomarkers of atherosclerosis.Firstly,an analytical method for Lyso-PLs was established based on UPLC-QTRAP-MS/MS and fully validated.Secondly,169targeted Lyso-PLs in plasma samples of ApoE^-/-mice and their littermates collected at different stages of atherosclerosis were quantified.Finally,12 Lyso-PLs were identified as more reliable biomarkers by integrating time-resolved analyses and static metabolomics.2.Study on the connection between sphingosine 1-phosphate and the occurrence of stroke.Sphingosine 1-phosphate?S1P?is a sphingomyelin metabolite that can maintain the integrity of the blood-brain barrier and increase its permeability at the same time.Therefore,accurate quantification of S1P is vital for studying the relationship between S1P and the pathology of stroke.In this study,a quantification method for S1P in human plasma was established and validated based on LC-QTRAP-MS/MS.Using this method,S1P in plasma samples of acute cerebral infarction patients?n=47?,acute cerebral hemorrhage patients?n=11?and healthy controls?n=22?were quantified,and the average concentrations were 196 ng/mL,161 ng/mL,and 234 ng/mL,respectively.Subsequently,the data from each group were analyzed by One-Way ANOVA.The results showed that the plasma level of S1P in the cerebral infarction group and the cerebral hemorrhage group was significantly lower than that of the control group.According to the receiver operating characteristic curve?ROC?analysis,the cut-off value of S1P concentration distuiguishing the cerebral infarction group and control group was 229 ng/mL,and the cut-off value of S1P concentration distuiguishing the cerebral hemorrhage group and control group was 219 ng/mL.