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Percutaneous Coronary Intervention (PCI) Reprograms Circulating Extracellular Vesicles from ACS Patients Impairing
Saveria Femminò1, Fabrizio D'Ascenzo2, Francesco Ravera1
1Department of Medical Sciences, University of Turin, 10126 Turin, Italy.
International Journal of Molecular Sciences
|October 13, 2021
Summary
Percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients impairs the cardio-protective effects of extracellular vesicles (EVs). EVs collected after PCI lost their protective properties, highlighting a critical need for further research into EV-based therapies for cardiovascular disorders.
Area of Science:
- Cardiovascular Research
- Extracellular Vesicle Biology
- Regenerative Medicine
Background:
- Extracellular vesicles (EVs) show therapeutic potential for cardiovascular diseases.
- Previous studies indicated EVs from Acute Coronary Syndrome (ACS) patients undergoing sham procedures were cardio-protective, while those from Remote Ischemic Pre-conditioning (RIPC) were not.
- No data existed on EVs from ACS patients post-Percutaneous Coronary Intervention (PCI).
Purpose of the Study:
- To investigate the cardio-protective properties of EVs collected from ACS patients after PCI.
- To compare EVs from RIPC (EV-RIPC) and sham (EV-naive) procedures post-PCI.
- To assess the impact of PCI on EV cargo and function.
Main Methods:
- EVs were collected from 30 ACS patients randomized to RIPC or sham procedures post-PCI.
- EVs were characterized using Transmission Electron Microscopy (TEM), Flow Cytometry (FACS), and Western blot.
- mRNA content was analyzed, and the impact of EVs on hypoxia/reoxygenation damage and Ischemia/Reperfusion Injury (IRI) was evaluated in vitro and ex vivo.
Main Results:
- Both EV-naive and EV-RIPC failed to provide cardio-protection in vitro and ex vivo.
- EV treatment did not activate canonical cardio-protective signaling pathways.
- PCI reduced Dusp6 mRNA in EV-naive and upregulated stress-related genes in EV-RIPC, indicating altered EV cargo.
Conclusions:
- PCI significantly reprograms the cargo of EVs in ACS patients.
- Post-PCI EVs exhibit impaired cardio-protective properties compared to pre-PCI EVs.
- Current EV-RIPC strategies do not enhance functional capabilities post-PCI in ACS patients.
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