Potential Applications and Functional Roles of Exosomes in Cardiometabolic Disease

Abstract

Despite diagnostic and therapeutic advances, cardiometabolic disease remains the leading cause of death worldwide. Extracellular vesicles (EVs), which include exosomes and microvesicles, have gained particular interest because of their role in metabolic homeostasis and cardiovascular physiology. Indeed, EVs are recognized as critical mediators of intercellular communication in the cardiovascular system. Exosomes are naturally occurring nanocarriers that transfer biological information in the setting of metabolic abnormalities and cardiac dysfunction. The study of these EVs can increase our knowledge on the pathophysiological mechanisms of metabolic disorders and their cardiovascular complications. Because of their inherent properties and composition, exosomes have been proposed as diagnostic and prognostic biomarkers and therapeutics for specific targeting and drug delivery. Emerging fields of study explore the use exosomes as tools for gene therapy and as a cell-free alternative for regenerative medicine. Furthermore, innovative biomaterials can incorporate exosomes to enhance tissue regeneration and engineering. In this work, we summarize the most recent knowledge on the role of exosomes in cardiometabolic pathophysiology while highlighting their potential therapeutic applications.

Perivascular adipose tissue and adipocyte-derived exosomal miRNAs maintain vascular homeostasis

“…The biogenesis and release of PVAT-derived adipocyte exosomes share biological mechanisms similar to the general cellular exosome release [ [31] , [32] , [33] ]. In general, proteins like tetraspanins and components of the endosomal sorting complex required for transport (ESCRT) are pivotal to exosome biosynthesis in adipocytes [ [31] , [32] , [33] ] ( Fig. 2 ).…”

“…Tetraspanins (CD9, CD63, CD81, and CD82) are exosomal membrane-enriched transmembrane proteins that serve as marker proteins for vesicles [ 31 , 37 ]. Tetraspanins are involved in mediating the biogenesis of ILVs and sorting and releasing exosomal cargo from MVBs [ 32 ]. These proteins can form a four-transmembrane scaffold that mediates the interaction of the bilayer with other proteins, promoting the budding process [ 32 , 38 ].…”

“…Tetraspanins are involved in mediating the biogenesis of ILVs and sorting and releasing exosomal cargo from MVBs [ 32 ]. These proteins can form a four-transmembrane scaffold that mediates the interaction of the bilayer with other proteins, promoting the budding process [ 32 , 38 ]. Finally, sphingomyelinases, Rab GTPases (such as Rab27a, Rab2b, Rab5a, and Rab91), and soluble N-ethylmaleimide-sensitive factor activating protein receptor (SNARE) proteins mediate MVB fusion with the plasma membrane and exosome release into the extracellular space during exosome secretion [ 31 , 39 ].…”

Scalable Production of Extracellular Vesicles and Its Therapeutic Values: A Review

“…EVs have emerged as informative biomarkers with the potential to become a valuable tool for the diagnosis and treatment monitoring of various diseases. EVs can be used as biological indicators for cardiometabolic diseases [ 66 , 67 , 68 , 69 ], neurological diseases [ 70 , 71 , 72 , 73 ], liver diseases [ 74 , 75 ], kidney diseases [ 76 ], respiratory diseases [ 77 ], skin diseases [ 2 , 78 ], and detection of graft rejection [ 79 ]. Small EVs from oral biofluids (i.e., saliva and gingival crevicular fluid) may act as biomarkers for diagnosing oral diseases noninvasively [ 80 , 81 ].…”

The potential value of exosomes as adjuvants for novel biologic local anesthetics

“…These results suggest the great potential of exosomes as anesthetic adjuvant drugs. Exosomes have also shown great potential in alleviating postoperative complications, such as reducing postoperative pain ( Cata et al, 2022 ), improving sleep, cognitive impairment ( Hsu et al, 2020 ; Gu and Zhu, 2021 ), and reducing the frequency of arrhythmias ( Poon et al, 2017 ; Ayala-Mar et al, 2021 ). Therefore, exploring specific sources of exosomes as anesthetic adjuvants may be a new avenue for future development of biological anesthetic adjuvants.…”