Injury minimization after myocardial infarction: focus on extracellular vesicles

Abstract

Despite improvements in clinical outcomes following acute myocardial infarction, mortality remains high, especially in patients with severely reduced left ventricular ejection fraction (LVEF <30%), emphasizing the need for effective cardioprotective strategies adjunctive to recanalization. Traditional cell therapy has shown equivocal success, shifting the focus to innovative cardioactive biologicals and cell mimetic therapies, particularly extracellular vesicles (EVs). EVs, as carriers of non-coding RNAs and other essential biomolecules, influence neighbouring and remote cell function in a paracrine manner. Compared to cell therapy, EVs possess several clinically advantageous traits, including stability, ease of storage (enabling off-the-shelf clinical readiness), and decreased immunogenicity. Allogeneic EVs from mesenchymal and/or cardiac stromal progenitor cells demonstrate safety and potential efficacy in preclinical settings. This review delves into the translational potential of EV-based therapeutic approaches, specifically highlighting findings from large-animal studies, and offers a synopsis of ongoing early-stage clinical trials in this domain.

Evolving Strategies for Extracellular Vesicles as Future Cardiac Therapeutics: From Macro- to Nano-Applications

“…When injected into infarcted rat hearts, they counteracted resident cardiomyocyte apoptosis, enhanced cardiac function, and supported local angiogenesis [75]. Similar results were validated in a large animal model, wherein intracoronary delivery of hCPC-EV reduced the infarct size in porcine acute myocardial infarction [94,95]. hCPC-EVs were also tested in preclinical murine models of doxorubicin/trastuzumab-induced cardiotoxicity.…”

“…Although EV-based cardiac therapy has generally been deemed safe, recent concerns have emerged regarding possible pro-arrhythmogenic complications, which still require systematic evaluation. Nonetheless, recent evidence indicates that EV treatment should not significantly increase the risk of arrhythmia predisposition [ 95 ]. The optimization of EV-cardiac delivery and targeting is a rapidly evolving research field.…”

Non-coding RNA yREX3 from human extracellular vesicles exerts macrophage-mediated cardioprotection via a novel gene-methylating mechanism

“… 1 Extracellular vesicles (EVs) have recently come to the fore as a new category of cardioprotective agents that may, at least in principle, work in a manner adjunctive to PCI. 2 , 3 We became interested in EVs, as they mediate the disease-modifying bioactivity of cardiosphere-derived cell (CDC) therapy for MI 3–5 and Duchenne muscular dystrophy. 6 , 7 Extracellular vesicles produced by CDCs (CDC-EVs) contain >10 000 molecularly distinct non-coding RNA (ncRNA) entities with plausible but uncharacterized bioactivity.…”