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.
Highlights
Intercellular communication, an essential facet of cellular function, is achieved through a highly organized and unique system involving signaling molecules
Due to a lack of conclusive literature explaining the origin and function of apoptotic bodies, in this review, we focus on exosomes and MVs as potential therapeutic vehicles to treat cardiovascular disease (CVD)
In the absence of all endosomal sorting complexes required for transport (ESCRT) complexes, exosome biogenesis depends on lipids such as ceramide, lysobisphosphatidic acid (LBPA) and tetraspanins (CD63, CD9, CD81, CD82, and CD151) that are crucial for membrane remodeling, budding and protection from hydrolases in the extracellular environment [29,44,45,46,47,72]
Summary
Intercellular communication, an essential facet of cellular function, is achieved through a highly organized and unique system involving signaling molecules. Most cell types orchestrate a highly coordinated packaging of biochemical signals in membrane-bound vesicles called extracellular vesicles (EVs) that are ubiquitously secreted to extracellular milieu [1,2,3,4]. The emerging roles of EVs in intercellular communication, disease pathogenesis and diagnosis have increased interest in investigating their potential to serve as a therapeutic vehicle [1,5,9,10,11]. Despite accrual of scientific evidence highlighting the function of EVs and their therapeutic potential, we do not have a comprehensive understanding of the mechanisms of their origin and secretion. We will discuss current EV engineering methods employed to deliver therapeutic molecules, and the applications of this technology in CVD treatment
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