P2580Changes in extracellular vesicles during and after STEMI and potential influences of remote ischemic conditioning
Authors: Haller P , Jaeger B , Piackova E , Sztulman L , Spittler A , Wojta J , Kiss A , Podesser B K , Huber K 
Published: October 2019

Background

Due to their role in transportation of different molecules, such as microRNAs and mRNAs, extracellular vesicles (EVs) enable inter-cellular communication. Therefore, they are potential biomarkers in several kinds of disease. Information on their kinetics during acute and subacute ST-elevation myocardial infraction (STEMI) is limited and potential influence of remote ischemic conditioning (RIC) has not been investigated in humans so far.

Methods

We conducted a randomized, controlled trial in patients with first-ever STEMI; all patients received primary percutaneous coronary intervention (PCI). Additionally, the interventional group received a protocol of RIC (5 min inflation of a blood pressure cuff on the left upper arm to 200mmHg, 5 min deflation, 4 repetitions in total), whereas controls received sham-intervention (cuff placement). Citrate-plasma for EV analysis was taken prior to (baseline) and immediately after PCI, as well as after 24 hours, 4 days and 1 months. EVs were characterized by a high-sensitive flow cytometer using fluorescence-triggering. EVs were defined as being positive for the intra-vesicular marker CalceinAM or superficial expression of phosphatidylserine (PS; target of Lactadherin) in addition to another superficial epitope. Mixed-models were used to investigate changes over time; time and RIC were treated as fixed effects, patients were treated as random effects to account for the multiple testing design.

Results

We included 32 patients (16 RIC, 16 control). There was a significant impact of RIC on the changes in platelet (CD41) EVs from baseline (P=0.03, Figure). Furthermore, pro-coagulatory platelet EV (PS+/CD41+) were influenced by time after STEMI (after PCI P=0.017; 24h P=0.005) with significant interaction with RIC immediately and 24h after PCI (P for interaction of time with RIC; after PCI P=0.024, after 24h P=0.008). Likewise, monocyte (CD14) EVs increased significantly with time (4 days P=0.005, 1 Month P<0.001) with significant reduced levels of monocyte EVs by RIC at these time points (P for interaction at 4 days = 0.0493; and 1 month <0.001). There was also a significant change from baseline without any effect of RIC observed in inflammatory/leucocyte EVs (CD66b+; P for change from baseline for all time points <0.001). Pro-coagulatory and inflammatory (PS+/CD15+) EVs were significantly reduced over time (at 24h P=0.007; at 4 days P=0.049, at 1 month P=0.002). Finally, endothelial (CD31+/CD41-) EVs were significantly increased at 1 month after STEMI (P=0.032).

Conclusion

Several circulating EV sub-population are influenced by the acute phase of STEMI. RIC significantly impacts on the changes in platelet EVs during the initial phase after STEMI. Future studies are needed to clarify the functional importance of theses changes and whether this influence is part of a cardioprotective effect of RIC.

Acknowledgement/Funding

LBC for Cardiovascular Research Vienna; ATVB Vienna, a grant of the “Medical Scientific Fund of the Mayor of the City of Vienna”