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Extracellular Vesicles in Angiogenesis
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Edité par CCSD ; American Heart Association -
Review. A ngiogenesis, defined as the formation of new blood vessels from a pre-existing vascular network, naturally occurs in an organism during growth and development and also in response to injury to restore a tissue's blood supply and promote wound healing. The new vessels can be formed by either sprouting angiogenesis, where endothelial cells (ECs) form sprouts that grow toward an angiogenic stimulus, or intussus-ceptive angiogenesis, where interstitial tissues invade the existing vessels and form transvascular tissue pillars that expand and split the vessel. 1 Sprouting angiogenesis comprises several steps: enzymatic degradation of the vessel's basement membrane , EC proliferation, migration, sprouting, branching, and tube formation. The stabilization and maturation of the newly formed vascular structures require the recruitment of pericytes, the deposition of extracellular matrix, and mechanical stimulation by the shear stress. In healthy tissues, angiogenesis is tightly regulated by a precise balance between stimulatory and inhibitory signals. 2 Abnormal blood vessel growth occurs when this balance is disturbed and is a major cause of numerous diseases, such as cancer, atherosclerosis, corneal neovas-cularization, rheumatoid arthritis, or ischemic diseases. During the past decade, the vesicles released by different cell types have been shown to be important mediators during the process of blood vessel formation and, as such, they have attracted particular interest among researchers from various fields of biology and medicine, including angiogenesis. 3,4 Longtime considered as inert debris or a hallmark of cell injury, extracellular vesicles (EVs), which include apoptotic bodies, microvesicles, and exosomes, have emerged as an important tool for intercellular communications in normal physiology and in pathophysiological conditions. 5,6 Indeed, EVs function as the carriers of small bioactive molecules, such as Review Circulation Research is available at http://circres.ahajournals.org Abstract: During the past decade, extracellular vesicles (EVs), which include apoptotic bodies, microvesicles, and exosomes, have emerged as important players in cell-to-cell communication in normal physiology and pathological conditions. EVs encapsulate and convey various bioactive molecules that are further transmitted to neighboring or more distant cells, where they induce various signaling cascades. The message delivered to the target cells is dependent on EV composition, which, in turn, is determined by the cell of origin and the surrounding microenvironment during EV biogenesis. Among their multifaceted role in the modulation of biological responses, the involvement of EVs in vascular development, growth, and maturation has been widely documented and their potential therapeutic application in regenerative medicine or angiogenesis-related diseases is drawing increasing interest. EVs derived from various cell types have the potential to deliver complex information to endothelial cells and to induce either pro-or antiangiogenic signaling. As dynamic systems, in response to changes in the microenvironment, EVs adapt their cargo composition to fine-tune the process of blood vessel formation. This article reviews the current knowledge on the role of microvesicles and exosomes from various cellular origins in angiogenesis, with a particular emphasis on the underlying mechanisms, and discusses the main challenges and prerequisites for their therapeutic applications. (Circ Res.
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