Therapeutic and Diagnostic Translation of Extracellular Vesicles in Cardiovascular Diseases

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  Figure 1.. Formation, characterization, and secretion of various extracellular vesicles such as microvesicles, exosomes, and apoptosomes. Blue indicates extracellular compartment; red indicates intracellular compartment; and yellow indicates acidic compartment. Note that organelle proportions are not to scale. EV indicates extracellular vesicles; ILV, intraluminal vesicles; L, lysosome; MVB, multivesicular bodies; PM, plasma membrane; RER, rough endoplasmic reticulum; and TGN, trans-Golgi network.

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  Figure 2.. Mechanisms of EV-mediated local and distal communications of the heart. Local communication within the heart is mediated by crosstalk between different cell types via EV secretion as indicated by arrows (paracrine manner). Different cardiac cell types secrete EVs that may also function in an autocrine manner affecting the same cell that released the vesicles. On the other hand, distant communication is mediated by secretion of EVs from the myocardium into the systemic circulation, mediating functional crosstalk between the heart and other organs (eg, bone marrow). Myocardial local and distal communications involve exchange of proteins, lipids, and nucleic acids shuttled via EVs between cells through endocytosis, membrane fusion, or gap junction–mediated transfer. Mechanisms by which EVs function additionally include receptor-mediated signaling leading to regulation of transcription and posttranscriptional processes in the target cell. Because of these capabilities, EVs were shown to be effective communicators of biological signaling implicated in multiple processes governing cardiac function under normal cardiac physiology as well as in disease. CM indicates cardiomyocyte; CSC,…

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  Figure 3.. EV diagnostics and various strategies for EV-based therapies. Diagnostics: EVs carry bioactive molecules from their host cells that are indicative of pathophysiological conditions, and they are considered to be crucial for biomarker discovery for clinical diagnostics. Therapeutics: EVs can be isolated directly from body fluid and tissue or indirectly from in vitro cultured cells. Cell modification by genetic or metabolic engineering can lead to the release of modified EVs. Alternatively, EVs can be modified directly using chemical treatment or scaffolding strategies. BAL indicates bronchoalveolar lavage; and EV, extracellular vesicles.