An extracellular vesicle epitope profile is associated with acute myocardial infarction

Abstract

The current standard biomarker for myocardial infarction (MI) is high‐sensitive troponin. Although powerful in clinical setting, search for new markers is warranted as early diagnosis of MI is associated with improved outcomes. Extracellular vesicles (EVs) attracted considerable interest as new blood biomarkers. A training cohort used for diagnostic modelling included 30 patients with STEMI, 38 with stable angina (SA) and 30 matched‐controls. Extracellular vesicle concentration was assessed by nanoparticle tracking analysis. Extracellular vesicle surface‐epitopes were measured by flow cytometry. Diagnostic models were developed using machine learning algorithms and validated on an independent cohort of 80 patients. Serum EV concentration from STEMI patients was increased as compared to controls and SA. EV levels of CD62P, CD42a, CD41b, CD31 and CD40 increased in STEMI, and to a lesser extent in SA patients. An aggregate marker including EV concentration and CD62P/CD42a levels achieved non‐inferiority to troponin, discriminating STEMI from controls (AUC = 0.969). A random forest model based on EV biomarkers discriminated the two groups with 100% accuracy. EV markers and RF model confirmed high diagnostic performance at validation. In conclusion, patients with acute MI or SA exhibit characteristic EV biomarker profiles. EV biomarkers hold great potential as early markers for the management of patients with MI.

Sphingolipid composition of circulating extracellular vesicles after myocardial ischemia

“…Here, we provided additional sensitivity by quantifying sphingolipid species of circulating EV. In STEMI patients, systemic EV are mainly composed of vesicles that are released in the blood as result of acute thrombosis and inflammation 36 . Accordingly, we observed the expression of surface antigens from activated platelets (CD62p, CD41b, and CD42a), endothelium (CD31), and leukocytes (CD40), as previously described 36 .…”

“…After ultracentrifugation, purified EV were analysed by MACSPlex human Exosome Kit (Miltenyi, Bergisch Gladbach, Germany) with MACSQuant Analyzer-10 flow cytometer (Miltenyi, Bergisch Gladbach, Germany), as previously described 36,54 . EV samples were incubated overnight with capture-beads coated with specific antibodies for 37 EV surface antigens, and then with detection antibodies against CD9, CD63, CD81.…”

“…Linear discriminant analysis (LDA) was used as strategy for features reduction to build the canonical plot and evaluate the discrimination power of EV sphingolipid composition as signature to classify patients with STEMI. LDA employs linear combinations of variables to maximize the separation between groups by increasing precision estimates with variance reduction 36 . The algorithm computes a set of coefficients for linear combination of each variable to estimate the diagnosis.…”

EV-origin: Enumerating the tissue-cellular origin of circulating extracellular vesicles using exLR profile

“…Of note, the flow cytometry-based approaches play an important role in understanding the origins, functions, and diagnostic and therapeutic significance of EVs in health and disease [22] , [23] . Several studies have used flow cytometry analysis to trace platelet- and lymphocyte-derived EVs in circulation, these results indicated plasma EVs predominantly originated from platelets, erythrocytes, and other leucocytes [24] , [25] , [26] , [27] , [28] . While the EVs sorting techniques have been developed and applied clinically, comprehensive assessment of the heterogeneity of multiple tissue-cellular origins for circulating EVs remains challenging.…”

A Changing Paradigm in Heart Transplantation: An Integrative Approach for Invasive and Non-Invasive Allograft Rejection Monitoring

“…Vesicles from platelets, endothelial cells, monocytes, and leukocytes form the major component within the circulating exosomal fraction [ 54 ]. Furthermore, they are involved in immune responses, inflammation, and coagulation processes [ 55 , 56 , 57 ]. Hence, acute and chronic conditions affecting an altered inflammatory response are often associated with a systemic release of EVs containing specific proteins, nucleic acids, and/or lipids, conveying a distinct signature that is potentially relevant as a biomarker [ 56 , 57 ].…”