EV Cargo Sorting in Therapeutic Development for Cardiovascular Disease

Abstract

Cardiovascular disease remains the leading cause of morbidity and mortality in the world. Thus, therapeutic interventions to circumvent this growing burden are of utmost importance. Extracellular vesicles (EVs) actively secreted by most living cells, play a key role in paracrine and endocrine intercellular communication via exchange of biological molecules. As the content of secreted EVs reflect the physiology and pathology of the cell of their origin, EVs play a significant role in cellular homeostasis, disease pathogenesis and diagnostics. Moreover, EVs are gaining popularity in clinics as therapeutic and drug delivery vehicles, transferring bioactive molecules such as proteins, genes, miRNAs and other therapeutic agents to target cells to treat diseases and deter disease progression. Despite our limited but growing knowledge of EV biology, it is imperative to understand the complex mechanisms of EV cargo sorting in pursuit of designing next generation EV-based therapeutic delivery systems. In this review, we highlight the mechanisms of EV cargo sorting and methods of EV bioengineering and discuss engineered EVs as a potential therapeutic delivery system to treat cardiovascular disease.

Keywords: cardiovascular disease; cargo sorting pathogenesis; diagnostics; exosomes; extracellular vesicles; therapeutics.

Figure 1

A summary of (A) EV cargo sorting and (B) methods for engineering exosome-based therapeutics to treat cardiovascular disease. EV cargo sorting is dependent on recognition signal or motif, post-translational modifications, and signaling molecules via ESCRT-dependent or -independent mechanism. Current methods in engineering EVs to incorporate therapeutic molecules include viral (e.g., overexpression of a gene using a viral vector, and delivery of a gene using a recombinant virus) or non-viral (e.g., incorporation of drugs or bioactive compounds by incubation or mechanical means, and alteration of targeting peptides) approaches. Abbreviations: Extracellular Vesicle (EV), Endosomal Sorting Complex (ESCRT), Early Endosome (EE), Multivesicle (MV), Multivesicular body (MVB).