Plasma Exosome Profile in ST-Elevation Myocardial Infarction Patients with and without Out-of-Hospital Cardiac Arrest.

Marta Zarà,Elena Tremoli,Silvia Cerri,Daniela Trabattoni,Marco Biggiogera,Patrizia Amadio,Nicola Cosentino,Calogero Claudio Tedesco,Maria Luisa Biondi,Jeness Campodonico,Leonardo Sandrini,Emilio Assanelli,Gloria Milanesi,Fabio Blandini,Giancarlo Marenzi,Fabrizio Veglia,Silvia S Barbieri

doi:10.3390/ijms22158065

Abstract

The identification of new biomarkers allowing an early and more accurate characterization of patients with ST-segment elevation myocardial infarction (STEMI) is still needed, and exosomes represent an attractive diagnostic tool in this context. However, the characterization of their protein cargo in relation to cardiovascular clinical manifestation is still lacking. To this end, 35 STEMI patients (17 experiencing resuscitated out-of-hospital cardiac arrest (OHCA-STEMI) and 18 uncomplicated) and 32 patients with chronic coronary syndrome (CCS) were enrolled. Plasma exosomes were characterized by the nanoparticle tracking analysis and Western blotting. Exosomes from STEMI patients displayed a higher concentration and size and a greater expression of platelet (GPIIb) and vascular endothelial (VE-cadherin) markers, but a similar amount of cardiac troponin compared to CCS. In addition, a difference in exosome expression of acute-phase proteins (ceruloplasmin, transthyretin and fibronectin) between STEMI and CCS patients was found. GPIIb and brain-associated marker PLP1 accurately discriminated between OHCA and uncomplicated STEMI. In conclusion, the exosome profile of STEMI patients has peculiar features that differentiate it from that of CCS patients, reflecting the pathophysiological mechanisms involved in STEMI. Additionally, the exosome expression of brain- and platelet-specific markers might allow the identification of patients experiencing ischemic brain injury in STEMI.

Highlights

chronic coronary syndrome (CCS) patients (Figure 2), we found that the level of GPIIb was higher in exosome of OHCA-segment elevation myocardial infarction (STEMI) than in uncomplicated STEMI, whereas no difference in terms of fibronectin, VE-cadherin, ceruloplasmin and transthyretin expression was observed between the two STEMI groups (Figure 4a–e)
We show that circulating exosomes from STEMI patients have a different signature, in terms of number, dimension and specific protein cargo, compared to that of CCS patients
We found that the number and the size of circulating exosomes at hospital admission are significantly increased in STEMI patients as compared to CCS patients

Summary

Introduction

Recent attention has been given to exosomes as attractive diagnostic and prognostic tools in several clinical conditions [4], including cardiovascular diseases [5,6]. As exosomal release can be triggered by several stimuli associated with cellular stress [9,10,11,12,13,14], exosome secretion from platelets, vascular endothelial cells and brain cells, may be modulated in several pathological conditions, including myocardial infarction and stroke. The content of exosomes, representing a “fingerprint” of the releasing cell and its metabolic status, might be a rich source of biomarkers for various disease states [4,9,15]

Methods

Discussion

Conclusion