Abstract Number: PB0315
Meeting: ISTH 2021 Congress
Theme: Diagnostics and OMICs » Biomarkers of Thrombosis and Hemostasis
Background: Acute myocardial infarction (MI) with plaque rupture-induced thrombosis, coronary occlusion and subsequent ischemic injury, results in heart failure and is associated with poor prognosis. The emerging role of extracellular vesicles (EVs) in intercellular communication has stimulated renewed interest in exploring the potential application of EVs as tools for prognosis, and therapy in MI.
Aims: To analyze endogenous EVs proteome during MI and explore differences in EVs proteome from MI patients in relation to myocardial damage defined as left ventricular ejection fraction (LVEF).
Methods: 40 patients with MI, ST-elevation (STEMI) and non-ST-elevation (NSTEMI), were enrolled 2 days (mean) after the acute event. The EVs from plasma of patients and healthy controls (HC) were purified and characterized by Mass spectrometry based proteomic analysis. Proteins were identified and quantified using the database UniProt and software MaxQuant 1.5.1.2. The association between protein expression and continuous variables were analyzed using Spearman correlation test. For categorical variables, Wilcoxon rank sum test was used. The statistical analysis were made using R version 3.6.1. A p-value of <0.05 was considered statistically significant.
Results: 50 differentially expressed proteins from endogenous EVs were identified among MI patients compared to HC using MS analysis, of which 32 were up-regulated and 19 were down-regulated in MI patients as against HC. Statistical analysis comparing STEMI and NSTEMI patients revealed 4 differently expressed proteins. 22 proteins were found associated with LVEF function, when analyzed as a continuous variable, whereas 14 proteins were found to be differently expressed when LVEF was dichotomized in ≤ vs > 0.40 (Figure & Table).
Volcano plot for categorical variable of LVEF; Mean log2 difference vs individual p-values from Wilcoxon rank sum test, LVEF ≤ vs > 0.40
| Proteins within EVs | LVEF continuous variable | LVEF dichotomized in ≤ vs > 0.40 | Proteins within EVs | LVEF continuous variable | LVEF dichotomized in ≤ vs > 0.40 | Proteins within EVs | LVEF continuous variable | LVEF dichotomized in ≤ vs > 0.40 |
| Haptoglobin | X | Fibrinogen gamma chain | X | Alpha-a-antichymotrypsin | X | |||
| C-reactive protein | X | X | Apolipoprotein M | X | Inter-alpha-trypsin inhibitor heavy chain H3 | X | X | |
| C8A protein | X | Apolipoprotein C-III variant 1 | X | Alpha-1-acid glycoprotein 1 | X | |||
| Serum amyloid A protein | X | X | Ceruloplasmin | X | Epididymis secretory sperm binding protein | X | ||
| Serum amyloid A2 protein | X | Serotransferrin | X | GCT-A9 heavy chain | X | |||
| Clusterin | X | APOL1 protein | X | X | GCT-A4 light chain variable region | X | ||
| Fibulin-1 | X | X | Transthyretin | X | Pigment epithelium-derived factor | X | ||
| Complement factor H-related protein 1 | X | X | Von Willebrand factor | X | X | Vinculin isoform CRA_c | X | |
| Complement component C9 | X | Lipopolysaccharide-binding protein | X | X | Filamin-A | X | ||
| IgG H Chain | X |
Differently expressed EV proteins as defined in relation to LVEF
Conclusions: Endogenous EVs from patients with recent MI with reduced LVEF harbor proteins known associated with heart failure as well as several other proteins that demand further investigation to define whether they actively modulate myocardial function or present as a result of the myocardial damage upon ischemia.
To cite this abstract in AMA style:
Khandagale A, Bergström Lind S, Shevchenko G, Westerbergh J, Lindahl B, Siegbahn A, Christersson C. Proteome Analysis of Extracellular Vesicles from Patients with Myocardial Infarction and Relation to Heart Function: An Observational Study [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/proteome-analysis-of-extracellular-vesicles-from-patients-with-myocardial-infarction-and-relation-to-heart-function-an-observational-study/. Accessed September 24, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/proteome-analysis-of-extracellular-vesicles-from-patients-with-myocardial-infarction-and-relation-to-heart-function-an-observational-study/