Harmonic Interplay of Angiogenic Growth Factors in the Development of Coronary Blood Vessels
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Organized blood vessel formation is essential for development and physiological function of organs. Blood vessel formation is composed of complicated and sequential processes initiated by vasculogenesis in which endothelial progenitor cells differentiate, proliferate, and subsequently assemble into primitive tubular networks.1 2 3 Vasculogenesis is followed by angiogenesis, wherein vascular networks remodel into more complex networks through dilatation, sprouting, and bridging.1 2 3 Another form of blood vessel growth after birth is arteriogenesis. Arteriogenesis is defined as structural enlargement and remodeling by growth of preexisting arteriolar connections.2 3 4 During arteriogenesis, smooth muscle cells migrate and assemble along the preexisting tubes to form mature, stabilized vessels with vasomotor functions.2 3 4 Although vasculogenesis has been observed solely in the embryonic stage, the identification of circulating endothelial precursor cells indicates the contribution of vasculogenesis in blood vessel formation in adult tissue.5
Coronary blood vessels originate from endothelial precursor cells migrating to the epicardium in the embryonic stage, during which coronary vasculogenesis takes place.6 7 The vascular tubes formed by vasculogenesis grow by angiogenic sprouting and mature in the interaction with pericytes. The result is coronary capillary formation. After capillary formation, vascular plexuses, which appear in the outflow tract region, generate continuous tubes and penetrate into the aorta. Along these preexisting vessels, recruited smooth muscle cells migrate and cover the tubes from epicardial to endocardial direction. Then vessels form coronary veins and arteries.6 7 During the early postnatal period, marked capillary growth proceeds in myocardium, and maturation of arteries occurs mostly after birth.6 7
Because most of the works in this field have focused on polypeptide angiogenic factors until recently, angiogenic growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), have been highlighted as key regulators of blood vessel formation …