Angiogenesis is defined in medical dictionaries as "the development, formation and differentiation of new blood vessels" and plays a key role in human physiology. The terms "angio- or angi-" corresponds to "blood or lymph vessels" and the term "genesis" corresponds to "production of" and therefore "angiogenesis" corresponds to "development or production of new blood vessels". Angiogenesis is a physiological process through which new blood vessels are formed from pre-existing vessels. The meaning of the term "vasculo" is "a blood vessel" and "vasculogenesis" describes the de novo formation or new formation of the vascular system of endothelial cells from mesoderm cell precursor cells. The mesoderm is one of the three germ layers of the very early embryo. The other two layers are the ectoderm or outside germ layer and the endoderm or inside germ layer. The mesoderm is the middle layer between the ectoderm and the endoderm. Endothelial cells are thought to arise from the splanchnopleuric mesoderm, a structure created during the development of the embryo when the lateral mesodermal germ layer splits into two layers, and form the inner lining of a blood vessel. These cells provide an anticoagulant barrier between the vessel wall and blood. Endothelial cells function as a selective permeability barrier in which the endothelial cells act as unique multifunctional cells with critical basal and inducible metabolic and synthetic functions. Furthermore, angiogenesis is a vital process in normal growth and development, in wound healing and in the formation of granulation tissue. It is also involved in the transition of tumors from a benign state to a malignant state. In recent years, it has also become evident that angiogenesis is relevant in the genesis of diabetic retinopathy and growth of several tumors. The last decade has seen increased research to describe the various signals and pathways that define angiogenesis. These include a number of growth factors, receptors, redox states, and pro-inflammatory states. The use of microarray technologies allowed confirmation postulation of novel angiogenesis pathways.
Cells involved in angiogenesis pathways respond to hormones, some of which are peptides. These hormones act as chemical mediators regulating the growth, motility, function, and survival of the cells. Angiogenesis hormones act either directly on endothelial cells or indirectly by regulating proangiogenic factors. Proteins and peptides of the growth hormone / prolactin / placental lactogen, the rennin-angiotensin, and the kallikrein-kinin system can acquire antiangiogenic properties after proteolytic cleavage or activation. Furthermore, multiple factors and molecules are involved in balancing angiogenesis. The actions of angiongenic peptide hormonal families determine the outcome of health and disease.
The following peptide hormones are known to have angiogenic or antiangiogenic actions.
Angiogenic action:
Adrenocorticotropic hormone (ACTH), also known as corticotrophin, adrenomedullin, angiotensin II, bradykinin, calcitonin, endothelin, erythropoietin, gastrin, gonadotropins, growth hormone/prolactin/placental lactogen, growth hormone-releasing hormone, insulin, insulin-like growth factor 1 (IGF-1), also called somatomedin C, leptin, neuropeptide Y, oxytocin, parathyroid hormone, relaxin, thrombopoietin, thyroid-stimulating hormone, and vasopressin.
Antiangiogenic action:
Angiotensin-(1-7), angiotensinogen, cleaved high-molecular-weight kininogen, des-angiotensin I-angiotensinogen, ghrelin, gonadotropin-releasing hormone, natriuretic peptides, somatostatin,
And vasoinhibins.
Pro- and antiangiogenic actions:
Adiponectin, and corticotropin-releasing hormone.
Receptors:
The VEGF family of signaling molecules is now known to stimulate vasculogenesis in embryos and angiogenesis in adults.
The list of known receptors includes VEGF-R, VEGF-R, PlGF-R; angiopoitin receptors Tie-1, and Tie-2, fibroblast growth factor receptor (FGF-R), platelet-derived growth factor receptor (PDGF-R), co-receptor for VEGFR NRP, co-receptor for VEGFR HSPG and isoforms of these receptors.
Cytokines in Angiogenesis:
Cytokines are involved in the regulation of angiogenesis, which is critical for normal vessel growth and ischemic tissue repair. It is thought that misregulation may lead to tumor progression and metastasis.
Neuropeptides and Angiogenesis:
Neuropeptides are ubiquitously expressed in different organs and in the peripheral nervous system, neuropeptides are secreted by the sensory and autonomic nerves. They participate in a wide range of functions including immune surveillance, cardiovascular homeostasis, regulation of endocrine function, cytokine and growth factor release, and importantly angiogenesis.
The list of these peptides includes neuropeptide Y, substance P, calcitonin gene-related peptide, vasoactive intestinal peptide, and somatostatin (SS). All of these neuropeptides are pro-angiogenic except SS, which has anti- angiogenic properties.
There many more molecular factors known to regulate angiogentic pathways such as integrins, hypoxia-inducible factors, mast cells, microRNAs, as well as others.
Presently insufficient information concerning the regulation of angiogenesis by different molecular factors is available. To clearly understand the regulatory pathways of angiogenesis, in normal and cancerous tissue, in-depth studies are needed to address the consequences for misregulation of all the parts in the involved pathways including new types of microDMAs that maybe identified in the future.
References
Carmen Clapp , Stéphanie Thebault , Michael C. Jeziorski , Gonzalo Martínez De La Escalera; Peptide Hormone Regulation of Angiogenesis. Physiological Reviews Published 1 October 2009Vol. 89no. 1177-1215. DOI: 10.1152/physrev.00024.2009
Advances in Biochemistry in Health and Disease. Biochemical Basis and Therapeutic Implications of Angiogenesis. Jawahar L. Mehta, Naranjan S. Dhalla. Editors. ISBN 978-1-4614-5856-2 ISBN 978-1-4614-5857-9 (eBook) DOI 10.1007/978-1-4614-5857-9
Springer New York Heidelberg Dordrecht London.
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04/06/2014