Identification Of Differentially Expressed Proteins In Bicuspid Aortic Valve Patients With Acute Aortic Dissection Based On DIA Quantitative Proteomics Technology

Objective: Bicuspid aortic valve（BAV）is a common congenital valve disease in the department of cardiovascular surgery.It is often associated with a range of aortic diseases.Aortic dissection,one of the many complications of BAV,is known for its rapid onset and high mortality rate.It is a serious threat to patients’ lives and greatly influences patients’ treatment and prognosis.Early diagnosis of the disease is therefore extremely important and specific biomarkers are urgently needed.This paper aims to investigate the differentially expressed proteins in BAV patients with acute aortic dissection using proteomics technology,in order to identify molecular mechanisms of the disease and to select the differentially expressed proteins that are closely related to the disease,which will provide theoretical guidance for early diagnosis and targeted therapy of the disease in the future.Methods: Five patients with both BAV and acute type A aortic dissection and six BAV patients who were treated surgically at the Department of Cardiovascular Surgery,the First Affiliated Hospital of Anhui Medical University were recruited for this study.We performed a proteomic analysis of the tissue of aortic wall from these11 patients,using mass spectrometry and DIA quantitative proteomics technology to characterize and quantify all the proteins we obtained,from which we identified many differentially expressed proteins with significant expression levels,and also selected some of them that are closely related to the disease and can be used as biomarkers.Bioinformatics analysis was also conducted for these differentially expressed proteins.Gene Ontology（GO）analysis was used to annotate and functionally classify the differentially expressed proteins.The Kyoto Encyclopedia of Genes and Genomes（KEGG）and STRING network databases were used to systematically analyze the functions of differentially expressed proteins,in order to identify the signaling pathways involved in these differentially expressed proteins and the interrelationships among all proteins,and thus to understand the range of biological processes in which these differentially expressed proteins are involved and the biological functions they have.Results: The study found that the patients in the experimental group were younger,had lower systolic and diastolic blood pressure levels,and higher bilirubin,GGT,INR,D-dimer,maximum diameter of the aortic sinotubular junction and maximum diameter of the ascending aorta levels compared to the control group,both of which were statistically significantly different.Through DIA proteomics method,we identified a total of 948 differential proteins,of which 467 were upregulated and 481 were downregulated.GO analysis and KEGG analysis showed that these differentially expressed proteins are involved in a variety of signaling pathways,such as the spliceosome pathway,the oxidative phosphorylation pathway,the ECM-receptor interaction pathway,and the focal adhesion pathway.These differentially expressed proteins are also involved in a variety of biological activities,with oxidative phosphorylation and ECM structural constituent being the most significant biological activities.Eventually,we screened 10 differentially expressed proteins that are closely related to the pathogenesis of the disease and can be used as biomarkers for the diagnosis of the disease: PPP2R1 A,PDLIM3,PGAM1,DDAH2,PRKCSH,RAB8 A,NT5E,FLNC,C1 R,RPL4.Conclusion: In this study,we identified 10 differentially expressed proteins which are closely related to the pathogenesis of the disease through DIA quantitative proteomics technique.The discovery of these differentially expressed proteins may provide theoretical guidance for future research on the pathogenesis,early diagnosis,and treatment of the disease.