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

**Authors:** Yuye Wang, Haoran Li, Wanning Mou, Jiang Zhu

PMC · DOI: 10.1371/journal.pone.0343804 · 2026-03-10

## TL;DR

This study identifies plasma exosomal protein ITIH4 as a potential early biomarker for acute myocardial infarction using proteomics and validation techniques.

## Contribution

The study introduces ITIH4 as a novel exosomal biomarker for early detection of acute myocardial infarction.

## Key findings

- 24 differentially expressed proteins were identified in AMI patients.
- Exosomal ITIH4 showed significantly elevated expression in AMI patients.
- ITIH4 demonstrated high diagnostic accuracy with an AUC of 0.8825.

## Abstract

This study aimed to identify plasma exosomal protein biomarkers for early recognition of acute myocardial infarction (AMI) using label-free quantitative proteomics.

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.

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.

Plasma exosomal ITIH4 is closely associated with AMI and may serve as a promising early diagnostic biomarker.

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.

## Linked entities

- **Proteins:** ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4)
- **Diseases:** acute myocardial infarction (MONDO:0004781)

## Full-text entities

- **Genes:** MIR21 (microRNA 21) [NCBI Gene 406991] {aka MIRN21, hsa-mir-21, miR-21, miRNA21}, MIR208A (microRNA 208a) [NCBI Gene 406990] {aka MIR208, MIRN208, MIRN208A, hsa-mir-208a, miRNA208}, MIR126 (microRNA 126) [NCBI Gene 406913] {aka MIRN126, miRNA126, mir-126}, AMBP (alpha-1-microglobulin/bikunin precursor) [NCBI Gene 259] {aka A1M, EDC1, HCP, HI30, IATIL, ITI}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, C5AR1 (complement C5a receptor 1) [NCBI Gene 728] {aka C5A, C5AR, C5R1, CD88}, ITIH4 (inter-alpha-trypsin inhibitor heavy chain 4) [NCBI Gene 3700] {aka GP120, H4P, IHRP, ITI-HC4, ITIHL1, PK-120}, C8B (complement C8 beta chain) [NCBI Gene 732] {aka C82}, CANX (calnexin) [NCBI Gene 821] {aka CNX, IP90, P90}, APOC3 (apolipoprotein C3) [NCBI Gene 345] {aka APOCIII, Apo-C3, ApoC-3}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, PPBP (pro-platelet basic protein) [NCBI Gene 5473] {aka B-TG1, Beta-TG, CTAP-III, CTAP3, CTAPIII, CXCL7}, TNNI3 (troponin I3, cardiac type) [NCBI Gene 7137] {aka CMD1FF, CMD2A, CMH7, RCM1, TNNC1, cTnI}, HRG (histidine rich glycoprotein) [NCBI Gene 3273] {aka HPRG, HRGP, THPH11}, APOD (apolipoprotein D) [NCBI Gene 347], FGB (fibrinogen beta chain) [NCBI Gene 2244] {aka HEL-S-78p}, PLG (plasminogen) [NCBI Gene 5340] {aka HAE4}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CCN1 (cellular communication network factor 1) [NCBI Gene 3491] {aka CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10}, CD63 (CD63 molecule) [NCBI Gene 967] {aka AD1, HOP-26, ME491, MLA1, OMA81H, Pltgp40}, CD9 (CD9 molecule) [NCBI Gene 928] {aka BTCC-1, DRAP-27, MIC3, MRP-1, TSPAN-29, TSPAN29}, MIR183 (microRNA 183) [NCBI Gene 406959] {aka MIRN183, miR-183, miRNA183}, TSG101 (tumor susceptibility 101) [NCBI Gene 7251] {aka TSG10, VPS23}, CST3 (cystatin C) [NCBI Gene 1471] {aka ADLDWA, ARMD11, HEL-S-2}, VTN (vitronectin) [NCBI Gene 7448] {aka V75, VN, VNT}
- **Diseases:** heart failure (MESH:D006333), infarction (MESH:D007238), coronary artery disease (MESH:D003324), cardiac symptoms (MESH:D006331), cardiac remodeling (MESH:D020257), necrosis (MESH:D009336), bloodstream infections (MESH:D018805), UA (MESH:D000789), Staphylococcus aureus infection (MESH:D013203), coronary thrombus (MESH:D013927), metastasis (MESH:D009362), DEPs (MESH:D001039), atherosclerosis (MESH:D050197), death (MESH:D003643), Coronavirus disease - COVID-19 (MESH:D000086382), ischemic heart diseases (MESH:D017202), AMI (MESH:D009203), infections (MESH:D007239), coagulation dysfunction (MESH:D001778), cardiovascular and other diseases (MESH:D002318), coronary artery occlusion (MESH:D054059), chest discomfort (MESH:D013898), arrhythmias (MESH:D001145), ST-segment elevation myocardial infarction (MESH:D000072657), myocarditis (MESH:D009205), stroke (MESH:D020521), chest pain (MESH:D002637), myocardial injury (MESH:D009202), pulmonary embolism (MESH:D011655), stenosis (MESH:D003251), hemolysis (MESH:D006461), hypoxia (MESH:D000860), coronary artery stenosis (MESH:D023921), fibrosis (MESH:D005355), Disease (MESH:D004194), trauma (MESH:D014947), inflammation (MESH:D007249), ACS (MESH:D054058), coronary heart disease (MESH:D003327), aortic dissection (MESH:D000784), ischemic (MESH:D002545), malignancy (MESH:D009369), stable angina (MESH:D060050), renal failure (MESH:D051437), chronic kidney disease (MESH:D051436)
- **Chemicals:** PVDF (MESH:C024865), Glucose (MESH:D005947), creatinine (MESH:D003404), PBS (-), TG (MESH:D013866), phosphotungstic acid (MESH:D010772), water (MESH:D014867), iron (MESH:D007501), copper (MESH:D003300), Cholesterol (MESH:D002784), TC (MESH:D013667), EDTA (MESH:D004492), carbon (MESH:D002244), Triglycerides (MESH:D014280)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12974808/full.md

---
Source: https://tomesphere.com/paper/PMC12974808