Abstract
After myocardial infarction (MI), a strong inflammatory response takes place in the heart to remove the dead tissue resulting from ischemic injury. A growing body of evidence suggests that timely resolution of this inflammatory process may aid in the prevention of adverse cardiac remodeling and heart failure post-MI. The present challenge is to find a way to stimulate this process without interfering with the reparative role of the immune system. Extracellular vesicles (EVs) are natural membrane particles that are released by cells and carry different macromolecules, including proteins and non-coding RNAs. In recent years, EVs derived from various stem and progenitor cells have been demonstrated to possess regenerative properties. They can provide cardioprotection via several mechanisms of action, including immunomodulation. In this review, we summarize the role of the innate immune system in post-MI healing. We then discuss the mechanisms by which EVs modulate cardiac inflammation in preclinical models of myocardial injury through regulation of monocyte influx and macrophage function. Finally, we provide suggestions for further optimization of EV-based therapy to improve its potential for the treatment of MI.
Highlights
Cardiac macrophages had lower levels of iNOS, Arg1, and TNFα whereas IL-1β was increased in treated animals. This gene expression does not fit into the M1 or M2 classification, naïve bone marrowderived macrophages treated with Cardiosphere-derived cell (CDC)-Extracellular vesicles (EVs) in vitro showed higher phagocytic activity compared to M1 polarization control
It is generally accepted that EVs need to be internalized to exert their function on the recipient cells, it is unclear whether this is a requisite in monocytes and macrophages
The mechanisms by which EV cargo is delivered and how EVs avoid its degradation are still poorly understood [95]. It has become evident over the last decade that monocytes and macrophages play a central role in cardiac repair following myocardial infarction (MI), which makes them attractive therapeutic targets
Summary
Citation: Viola, M.; de Jager, S.C.A.; Sluijter, J.P.G. Targeting Inflammation and Joost P. G. Sluijter 1,2, *,† UMC Utrecht Regenerative Medicine Center, Circulatory Health Laboratory, University Utrecht, 3584 CS Utrecht, The Netherlands These authors contributed equally to this work.
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