Sprout synonym5/26/2023 ![]() When a sufficient number of filopodia on a given tip cell have anchored to the substratum, contraction of actin filaments within the filopodia literally pull the tip cell along toward the VEGF-A stimulus. The filopodia of tip cells are heavily endowed with VEGF-A receptors ( VEGFR2), allowing them to “sense” differences in VEGF-A concentrations and causing them to align with the VEGF-A gradient ( Figure 1.5). Long, thin cellular processes on tip cells called filopodia secrete large amounts of proteolytic enzymes, which digest a pathway through the ECM for the developing sprout. (B) The tip cells lead the developing sprout (more.)Īn endothelial tip cell guides the developing capillary sprout through the ECM toward an angiogenic stimulus such as VEGF-A. Hypoxic tissue is indicated by the circular blue fade. (A) Endothelial cells exposed to the highest VEGF-A concentration become tip cells (green). VEGF-A directed capillary growth to poorly perfused tissues. This process includes differentiation of mesodermal stem cells into angioblasts, growth factor directed migration of angioblasts to form blood islands where angioblasts give rise to endothelial cells. Vasculogenesis is a dynamic process that involves cell–cell and cell– extracellular matrix ( ECM) interactions directed spatially and temporally by – growth factors and morphogens. It occurs in the extraembryonic and intraembryonic tissues of embryos. Vasculogenesis ( Figure 1.2) is the de novo formation of blood vessels from angioblasts. Angioblasts are a cell type with potency to differentiate into endothelial cells but have not yet acquired all characteristic markers of endothelial cells. Hemangioblasts differentiate from mesodermal stem cells and give rise to hematopoietic stem cells and angioblasts. The luminal surface of the circulatory system in contact with blood is a single layer of endothelial cells: these are derived from mesoderm ( Figure 1.1). The cardiovascular system is the first organ system to develop in the embryo. For detailed histories of angiogenesis, see Refs. Recognition that control of angiogenesis could lead to cancer therapies stimulated intensive research in the field, e.g., only two manuscripts dealing with angiogenesis were published in 1970 and over 5200 articles were published in 2009. ![]() This belief is summarized in his Treatise published in 1794 as follows: “In short, whenever Nature has considerable operations going on, and those are rapid, then we find the vascular system in a proportionable degree enlarged.” Although the term angiogenesis does not appear in his writings, Hunter was the first to recognize that overall regulation of angiogenesis follows a basic law of nature founded by Aristotle, which in essence is “ form follows function.” The modern history of angiogenesis began with the work of Judah Folkman, who hypothesized (and published in 1971) that tumor growth is angiogenesis-dependent. His observations suggested that proportionality between vascularity and metabolic requirements occurs in both health and disease. The Scottish anatomist and surgeon John Hunter provided the first recorded scientific insights into the field of angiogenesis. Clearly, angiogenesis occurs throughout life. Capillaries grow in adipose tissue during weight gain and regress during weight loss. A lack of exercise leads to capillary regression. Exercise stimulates angiogenesis in skeletal muscle and heart. ![]() Capillaries grow and regress in healthy tissues according to functional demands. Decreasing or inhibiting angiogenesis can be therapeutic in cancer, ophthalmic conditions, rheumatoid arthritis, and other diseases. Stimulation of angiogenesis can be therapeutic in ischemic heart disease, peripheral arterial disease, and wound healing. Recognition that control of angiogenesis could have therapeutic value has stimulated great interest during the past 40 years. Hemodynamic factors are critical for survival of vascular networks and for structural adaptations of vessel walls. Oxygen plays a pivotal role in this regulation. Changes in metabolic activity lead to proportional changes in angiogenesis and, hence, proportional changes in capillarity. Capillaries are needed in all tissues for diffusion exchange of nutrients and metabolites. No metabolically active tissue in the body is more than a few hundred micrometers from a blood capillary, which is formed by the process of angiogenesis. It occurs throughout life in both health and disease, beginning in utero and continuing on through old age. Angiogenesis is the growth of blood vessels from the existing vasculature.
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