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Extracellular vesicles and Arrhythmogenic cardiomyopathy: new hopes

A comment by the ESC WG on Cellular Biology of the Heart

Treatment


Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disorder characterized by loss of cardiomyocytes, inflammation and fibrosis. Mutations in genes coding for intercellular junctions have been implicated in electrical conduction impairment leading to arrhythmia. Anti-inflammatory strategies have emerged as relevant therapeutic tools to tackle ACM. In this paper, resorting to an animal model with a mutation in desmoglein-2 that mimics ACM, Lin and colleagues show that extracellular vesicles (EV) secreted by immortalized cardiosphere-derived cells (CDC) mitigate some key pathological features of the disease. Indeed, the administration of EV improved cardiac function and diminished arrhythmia, by preserving the gap junction protein Cx43 at the intercalated disks, essential to ensure an efficient conduction of the electrical impulse (1). In addition, EV reduced cell death, inflammation and fibrosis, through a mechanism that at least partially relies on miR-4488.

This work highlights the impact of non-cellular therapeutic approaches, namely the use of EV as powerful and suitable treatment tools (2). Importantly, these therapeutic EV are secreted by immortalized and engineered cardiosphere-derived cells, which is relevant to enhance the large-scale production of vesicles and improve the reproducibility of the clinical approach. Furthermore, this study opens new avenues for the application of CDC-derived EV in other cardiovascular diseases with an inflammatory component.

References


1) Martins-Marques T, Hausenloy DJ, Sluijter JPG, Leybaert L, Girao H. Intercellular Communication in the Heart: Therapeutic Opportunities for Cardiac Ischemia. Trends Mol Med. 2021 Mar;27(3):248-262. doi: 10.1016/j.molmed.2020.10.002. 

2) Sluijter JPG, Davidson SM, Boulanger CM, Buzás EI, de Kleijn DPV, Engel FB, Giricz Z, Hausenloy DJ, Kishore R, Lecour S, Leor J, Madonna R, Perrino C, Prunier F, Sahoo S, Schiffelers RM, Schulz R, Van Laake LW, Ytrehus K, Ferdinandy P. Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology. Cardiovasc Res. 2018 Jan 1;114(1):19-34. doi: 10.1093/cvr/cvx211

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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