Extracellular Vesicles in Cardiovascular Diseases: Diagnosis and Therapy

FIGURE 1. Exosomes and MVs are both released by healthy cells. Exosomes are nanometer-sized vesicles of endocytic origin that form by inward budding of the limiting membrane of MVEs. MVs bud from the cell surface. Part of the endomembrane system in the cytoplasm includes the endoplasmic reticulum (ER), Golgi apparatus, and lysosomes, it helps to package proteins inside the cell through membrane-bound vesicles. Vesicles also allow exchanging membrane components with a cell’s plasma membrane. Similar to healthy cells, apoptotic cells can also release EVs (termed apoptotic extracellular vesicles, ApoEVs).

FIGURE 2. The general outlook of the EVs membrane composition and different molecular cargoes can markedly vary based on the parental cell and vesicle biogenesis.

FIGURE 3. Origins and roles of EVs in CVDs. EVs can be released by cardiovascular system-related cells, such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells (SMCs), leukocytes, monocytes, and macrophages. EVs mimic the cardioprotective properties by stimulating cell proliferation, improving cardiac survival, activating cell autophagy, promoting angiogenesis, enhancing neovascularization, decreasing cell apoptosis, reducing tissue fibrosis, preventing inflammation, inhibiting cardiovascular remodeling, treating myocardial infarction, reducing oxidative stress levels, and affecting immune cell polarization.

FIGURE 4. Modulation of EVs for CVDs therapy. Several strategies have been used to overcome the limitations of native EVs. To enhance the therapeutic potential of EVs, the membrane and the lumen have been functionalized. To track in vivo EVs, fluorophores, luminescence reporters, or radiotracers have been used to label formulations. To improve the targeting efficacy of EVs, exogenous peptides, proteins or lipids have been modified. To enhance EV internalization and endolysosomal escape, the vesicles have been modified with cationic lipids, pH-sensitive peptides, and cell-penetrating peptides.