Extracellular Vesicles in Angiogenesis

Angiogenesis, 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 intussusceptive angiogenesis, where interstitial tissues invade the existing vessels and form transvascular tissue pillars that expand and split the vessel. 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. Abnormal blood vessel growth occurs when this balance is disturbed and is a major cause of numerous diseases, such as cancer, atherosclerosis, corneal neovascularization, 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. 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. Indeed, EVs function as the carriers of small bioactive molecules, such as Review