Abstract
Rap1 signaling is important for both major processes of vessel formation: vasculogenesis, or de novo vessel formation, and angiogenesis, sprouting of new vessels from pre-existing ones. We provide an overview of genetic studies in mice and zebrafish and discuss some of the proposed underlying mechanisms derived from cellular models, with particular emphasis on Rap1's role in angiogenesis, maintenance of endothelial barrier and connection with cerebral cavernous malformation (CCM), a neurological deficit that leads to seizures and lethal stroke. Lastly, we provide a brief summary of studies in cardiac and smooth muscle cells, where the Epac-Rap1 signaling axis is emerging as an important regulator of contractility.
Keywords:
Angiogenesis; Cerebral cavernous malformations; Contractility; Endothelial junctions; Vasculogenesis.
© 2013 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Blood Vessels / metabolism*
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Blood Vessels / pathology
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Central Nervous System Neoplasms / blood supply
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Central Nervous System Neoplasms / genetics
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Central Nervous System Neoplasms / metabolism*
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Central Nervous System Neoplasms / pathology
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Endothelial Cells / metabolism*
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Endothelial Cells / pathology
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Endothelium, Vascular / metabolism*
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Endothelium, Vascular / pathology
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Gene Expression Regulation
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism
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Hemangioma, Cavernous, Central Nervous System / blood supply
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Hemangioma, Cavernous, Central Nervous System / genetics
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Hemangioma, Cavernous, Central Nervous System / metabolism*
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Hemangioma, Cavernous, Central Nervous System / pathology
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Mice
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Morphogenesis
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Neovascularization, Pathologic
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Neovascularization, Physiologic
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Signal Transduction*
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Zebrafish
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rap1 GTP-Binding Proteins / genetics
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rap1 GTP-Binding Proteins / metabolism*
Substances
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Epac protein, mouse
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Guanine Nucleotide Exchange Factors
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rap1 GTP-Binding Proteins