Proteomics-based biomarkers of plasma exosomes from patients with acute myocardial infarction

Abstract

Purpose This study aimed to identify plasma exosomal protein biomarkers for early recognition of acute myocardial infarction (AMI) using label-free quantitative proteomics. Methods Patients presenting to the Second Affiliated Hospital of Soochow University with chest discomfort between February 2022 and December 2022 were enrolled. Plasma exosomes from a discovery cohort (six AMI patients and six non-AMI controls) were analyzed by mass spectrometry. Differentially expressed proteins (DEPs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Candidate proteins were further validated by western blot (WB) in an independent validation cohort (20 AMI patients and 20 non-AMI controls). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic potential of the DEPs for AMI. Results A total of 24 DEPs were identified, of which 11 were upregulated and 13 were downregulated in AMI patients. WB analysis confirmed the significantly elevated expression of Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) in AMI-derived exosomes. The area under the ROC curve (AUC) for ITIH4 was 0.8825, indicating high diagnostic accuracy. Correlation analysis revealed a significant positive correlation between plasma exosomal ITIH4 levels and the level of cTnI expression (R = 0.702, P  < 0.001), indicates that exosomal ITIH4 may serve as a novel acute-phase reactant during myocardial injury. Conclusion Plasma exosomal ITIH4 is closely associated with AMI and may serve as a promising early diagnostic biomarker. Trial registration Registered at the Chinese Clinical Trial Registry ( https://www.chictr.org.cn/showproj.html?proj=149623 ) with No. ChiCTR2200056343 on February 4, 2022. Principal investigator: Jiang Zhu.