Changes in Circulating Extracellular Vesicles in Patients with ST-Elevation Myocardial Infarction and Potential Effects of Remote Ischemic Conditioning-A Randomized Controlled Trial.

Paul M Haller,Claudia Wegberger,Mariann Gyöngyösi,Bruno K Podesser,Kurt Huber,Edita Piackova,Andreas Spittler,Johann Wojta,Larissa Sztulman,Bernhard Jäger,Attila Kiss

doi:10.3390/biomedicines8070218

Abstract

(1) Background: Extracellular vesicles (EVs) have been recognized as a cellular communication tool with cardioprotective properties; however, it is unknown whether cardioprotection by remote ischemic conditioning (RIC) involves EVs. (2) Methods: We randomized patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) to additionally receive a protocol of RIC or a sham-intervention. Blood was taken before and immediately, 24 h, four days and one month after PCI. Additionally, we investigated EVs from healthy volunteers undergoing RIC. EVs were characterized by a high-sensitive flow cytometer (Beckman Coulter Cytoflex S, Krefeld, Germany). (3) Results: We analyzed 32 patients (16 RIC, 16 control) and five healthy volunteers. We investigated platelet-, endothelial-, leukocyte-, monocyte- and granulocyte-derived EVs and their pro-thrombotic sub-populations expressing superficial phosphatidylserine (PS+). We did not observe a significant effect of RIC on the numbers of circulating EVs, although granulocyte-derived EVs were significantly higher in the RIC group. In line, RIC had not impact on EVs in healthy volunteers. Additionally, we observed changes of PS+/PEV, EEVs and PS+/CD15+ EVs irrespective of RIC with time following STEMI. 4) Conclusion: We provide further insights into the course of different circulating EVs during the acute and sub-acute phases of STEMI. With respect to the investigated EV populations, RIC seems to have no effect, with only minor differences found for granulocyte EVs.

Highlights

Changes in clinical practice during the last decades have led to a substantial decline in mortality of patients with ST-elevation myocardial infarction (STEMI) [1]
PS granulocyte-derived EVs (GEVs) 24 h after percutaneous coronary intervention (PCI) (4.9% (95%CI 0.3–9.6), p = 0.039 Figure 3C), without any association with Remote ischemic conditioning (RIC)
In contrast to previous studies [33], we found no significant difference regarding the course of Endothelial-derived EVs (EEVs) during the acute phase after STEMI

Summary

Introduction

Changes in clinical practice during the last decades have led to a substantial decline in mortality of patients with ST-elevation myocardial infarction (STEMI) [1]. The resulting infarct size is strongly associated with morbidity and mortality following the acute event [4]. In this regard, the phenomenon of ischemia and reperfusion injury (IRI) describes an acute exacerbation of tissue damage upon reperfusion of the ischemic myocardium [5]. Several interventions directly targeting IRI have failed upon being tested in large-scale clinical randomized-controlled trials so far [6]. Interventions (i.e., (stem) cell therapy) targeting at a reduction of the infarct-induced myocardial scare in order to raise cardiac function have failed so far as well [7,8].

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Discussion

Conclusion