Angiogenesis of human retinal microvascular endothelial cells: Role of insulin-like growth factor-1 and hypoxia-inducible factor-1 alpha in the phosphatidylinositol 3-kinase pathway
Item
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Title
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Angiogenesis of human retinal microvascular endothelial cells: Role of insulin-like growth factor-1 and hypoxia-inducible factor-1 alpha in the phosphatidylinositol 3-kinase pathway
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Identifier
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d_2009_2013:d811d240bd28:11944
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identifier
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12601
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Creator
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Tachjadi, Janto,
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Contributor
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William J. L'Amoreaux
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Date
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2013
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Language
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English
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Publisher
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City University of New York.
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Subject
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Molecular biology | Neurosciences | Angiogenesis | HIF-1 alpha | Human retinal microvascular endothelial cells | IGF-1 | PI3K
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Abstract
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Retinal vascular formation is a complex process that requires a precise temporospatial regulation of various elements, including the growth factors. Insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) are ligands of specific receptor tyrosine kinases (RTKs), which, if activated, will initiate downstream pathways that ultimately promote cell survival, cell proliferation, vascular permeability and cell migration; all of which permit blood vessel development. Formation of blood vessels from pre-existing vessels may be normal (angiogenesis) or pathological (neovascularization) processes. Examples of required angiogenesis include wound healing and repair of the endometrium. In proliferative retinopathies, such as retinopathy of prematurity or diabetic retinopathy, there is a dysregulation of IGF-1 that results in the neovascular formation of abnormal retinal blood vessels from pre-existing vessels. In these proliferative retinopathies, neovascularization is intended to bring nutrients to tissues, with unfortunate risk of loss of vision. To add to the chemical mixture that promotes neovascularization, the transcription factor hypoxia-inducible factor (HIF) is important in inducing VEGF secretion in cells stimulated by either hypoxia or IGF-1. Therefore it is a convergence of several signaling pathways that ultimately leads to neovascularization. The goals of this thesis are to demonstrate the role of IGF-1 in the formation of retinal vasculature using human retinal microvascular endothelial (HRMVE) primary cell line; and to study the in vitro effect of IGF-1 stimulation on HIF-1alpha in human retinal angiogenesis through the phosphatidylinositol 3-kinase (PI3K) pathway.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biology
