Non-targeted Metabolomics Study In PAH Patients For Early Diagnosis And New Biomarkers’ Discovery

Introduction:Congenital heart disease-related pulmonary arterial hypertension is the most common cause of pulmonary hypertension in China,and its pathogenesis has not been fully elucidated.More effective and more universal treatment strategies are needed.Non-targeted metabolomics research has the ability to detect and analyze the target samples without relying on prior knowledge,which can be used for exploratory research on the role of special metabolites and metabolic pathways in disease occurrence.The aim of this study was to compare the plasma metabolites in superior vena cava and pulmonary artery in patients with or without pulmonary hypertension.The biological functions and metabolic pathways of plasma metabolites with great difference between two groups could be annotated by the metabolic database to find a worth-exploring metabolic pathway,providing clues for the early diagnosis,treatment and prognosis of pulmonary arterial hypertension.Method:The patients with congenital heart disease-related pulmonary hypertension,who were treated in Fuwai Hospital of Chinese Academy of Medical Sciences from 2016 to 2018,were the study group 1.Patients with idiopathic pulmonary hypertension were the study group 2,and patients with congenital heart disease without pulmonary hypertension were the control group.All the patients in these three groups were treated in the same period.Blood samples of superior vena cava and pulmonary artery were collected from each group by right cardiac catheterization.The differential metabolites in different groups of plasma were analyzed by LC-MS/MS.KEGG database was used for metabolic pathway enrichment analysis.The two methods are combined to explore the significant differences in metabolites and metabolic pathways that may be important for the occurrence and development of the disease.Conclusion:Metabolites such as glutamic acid in PAH patients’plasma had greatly changed,but also the corresponding metabolic pathways changed significantly.The discovery of these differential metabolites and potential metabolic pathways can provide some clues for early diagnosis and intervention of PAH.Targeted validation and functional studies of these compounds are still needed.