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Biological basis of angiogenesis and role of vascular endothelial growth factor-D
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
Within the embryo, pluripotent embryonic precursors differentiate into hemangioblasts which form blood islands. Cells at the periphery of blood islands differentiate into endothelial cells, while the cells in the center differentiate into hemopoietic precursors. Recently, it has been pointed out that there could be a common precursor for endothelial and smooth muscle cell precursors4. Embryonic stem cells in vitro can be induced to differentiate toward hemopoietic cells, endothelial cells or mural cells. Non-adherent cells will generate hemopoietic cells while adherent cells can be forced to differentiate into endothelial cells or smooth muscle cells if treated with different growth factors (Figure 1). Interestingly, specific substrates induce different percentages of one or another cell type, suggesting that integrin expression plays an important role in the differentiation pathways. The common precursors express markers like CD31, CD34 and the receptor Flk1/vascular endothelial growth factor receptor-2. Vasculogenesis is not restricted to the embryo. Bone marrow-derived angioblasts circulating can, following an induction program not yet understood, initiate a vasculogenesis process5.
Dopamine in the Immune and Hematopoietic Systems
Published in Nira Ben-Jonathan, Dopamine, 2020
The first blood vessels in the developing embryo are formed by vasculogenesis, defined as the differentiation of precursor cells (angioblasts) into endothelial cells and the de novo formation of a primitive vascular network. On the other hand, angiogenesis is the physiological process that is responsible for the formation of new blood vessels from preexisting ones. Angiogenesis plays critical roles in human physiology, ranging from reproduction and fetal growth to wound healing and tissue repair. The multistep process of angiogenesis is tightly regulated in a spatial and temporal manner by “on-off switch signals” between angiogenic factors, extracellular matrix components, and endothelial cells [69]. Uncontrolled angiogenesis may lead to several disorders, including vascular insufficiency (myocardial or critical limb ischemia) as well as vascular overgrowth (hemangiomas, vascularized tumors, and retinopathies). Thus, numerous therapeutic opportunities have been devised based on the understanding and subsequent manipulation of angiogenesis.
Human Liver Stem Cells:
Published in Gianfranco Alpini, Domenico Alvaro, Marco Marzioni, Gene LeSage, Nicholas LaRusso, The Pathophysiology of Biliary Epithelia, 2020
Strikingly, when the same cell population is treated under different conditions, principally including VEGF, they give rise to cells of endothelial lineage.70 Verfaillie therefore has additionally categorised them as angioblasts. However, they are reported to be AC133+,70 a marker previously ascribed to a sub-set of haematopoietic CD34 positive stem cells71 but which appears to be characteristic of endothelial cell progenitors, which leaves some confusion as to their true lineage and origin. Their relationship to mesenchymal (or stromal derived) stem cells, which are progenitors of tissue components such as bone, cartilage, the haematopoietic supporting stroma and adipocytes72 is not clearly defined.
Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations
Published in Expert Review of Hematology, 2023
Edwin Ocran, Nicholas L.J. Chornenki, Mackenzie Bowman, Michelle Sholzberg, Paula James
The formation and development of new blood vessels is a highly complex process involving several pathways and is achieved through two fundamental mechanisms, vasculogenesis and angiogenesis, which are essential for growth and repair of tissue. Vasculogenesis involves the differentiation of endothelial progenitor cells (EPCs), called angioblasts into endothelial cells, leading to the formation of a primordial vascular network [42]. Angiogenesis, on the other hand, involves the development of new capillaries from existing blood vessels and the remodeling and expansion of existing vascular networks [42]. Both vasculogenesis and angiogenesis play an important role during embryological development in utero. In adults, many physiological processes including wound healing and tissue repair are primarily through angiogenesis [43]. However, the recent identification of EPCs at sites of neurovascularization in animal models suggests that vasculogenesis plays a role in the development of blood vessels in the adult [44].
Ophthalmological Aspects of von-Hippel–Lindau Syndrome
Published in Seminars in Ophthalmology, 2021
Hashim Ali Khan, Muhammad Aamir Shahzad, Fatima Iqbal, Muhammad Amer Awan, Qaim Ali Khan, Ali Osman Saatci, Ahmed Abbass, Fazil Hussain, Syed Arif Hussain, Atif Ali, Wajahat Ali
The VHL gene is mapped to chromosome 3p25-p26. The VHL protein (pVHL) is involved in ubiquitination and degradation of hypoxia-inducible factor-1 alpha (HIF-1α) and hypoxia-inducible factor-2 alpha (HIF-2α) under normoxic conditions by serving as a substrate recognition subunit of ubiquitin ligase complex. Under normoxic conditions, the HIF is hydroxylated and binds to VHL protein and degraded rapidly; while under hypoxic conditions, HIF is stabilized and upregulated. Likewise, mutant copies of pVHL may cause escape and upregulation of HIF. HIF is a transcription factor and, when stabilized, enters the nucleus and recruits transcriptional coactivator complex p300/CBP, leading to upregulation/expression of hundreds of genes and triggering a cascade of angiogenesis and oncogenesis. Among the growth factors and cytokines upregulated by HIF signaling, transforming growth factor-alpha, epidermal growth factor (EGF) and its receptor (EGFR), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and erythropoietin (Epo) are involved in angiogenesis and tumorigenesis. These proteins are believed to play a role in the development of VHL tumors including RCH.1,4–13 Arrested angioblast cells, along with coexpression of Epo and EpoR, have been suggested to be the developmental origin of RCH and other CNS hemangioblastomas.1,4,7,8,14–31
Incorporating placental tissue in cord blood banking for stem cell transplantation
Published in Expert Review of Hematology, 2018
Luciana Teofili, Antonietta R. Silini, Maria Bianchi, Caterina Giovanna Valentini, Ornella Parolini
The formation of the embryonic vascular system involves vasculogenesis and angiogenesis. Vasculogenesis, or blood vessel formation, occurs in the embryo and extraembryonic membranes during the third week when mesenchymal cells differentiate into vessel-forming, endothelial-cell precursors called angioblasts, which gather to form isolated cell clusters called blood islands, which are associated with the umbilical vesicle or endothelial cords within the embryo. The blood islands form small cavities and angioblasts flatten into endothelial cells that align along the cavities in the blood islands to form the endothelium. Vasculogenesis occurs when the endothelium-lined cavities fuse to form networks of endothelial channels. Angiogenesis takes place when vessels sprout into adjacent areas by endothelial budding and fuse with other vessels. The mesenchymal cells that surround the primitive blood vessels differentiate into the muscular and connective tissue elements of the vessels.