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Vascular Endothelial Growth Factor‐A signaling in Bone Marrow‐Derived Endothelial Progenitor Cells Exposed to Hypoxia
Author(s) -
Hoffmann Brian Robert,
Wagner Jordan R.,
Prisco Anthony R.,
Greene Andrew S.
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.685.7
Subject(s) - angiogenesis , vascular endothelial growth factor , progenitor cell , microbiology and biotechnology , hypoxia (environmental) , signal transduction , vascular endothelial growth factor a , endothelial progenitor cell , bone marrow , chemistry , biology , immunology , cancer research , stem cell , vegf receptors , organic chemistry , oxygen
Bone marrow‐derived endothelial progenitor cells (BM‐EPCs) are stimulated by vascular endothelial growth factor A (VEGF‐A) and other pro‐angiogenic factors. VEGF‐A, a diffusible mitogen derived from the vasculature, plays a critical role in angiogenesis and an understanding of its signaling is valuable for treatment of peripheral vascular disease. During physiological angiogenesis, an increase in VEGF‐A expression stimulates endothelial tube formation and increases micro‐vessel density. Hypoxia is known to produce an enhanced angiogenic response and heightened levels of VEGF‐A are seen in oxygen deprived epithelial and endothelial cells. This study explores the influence of hypoxia on VEGF‐A signaling in rat BM‐EPCs through a novel approach for large‐scale mapping of signaling pathways utilizing VEGF‐A coupled to magnetic epoxy resin, cross‐linking, and tandem mass spectrometry. Signaling network analysis revealed proteins related to calcium signaling, nitric oxide signaling, cell cycle regulation, and inflammatory responses. Additionally, changes in BM‐EPC angiogenic tube formation in response to VEGF‐A during hypoxia was explored in conjunction with the pathway analysis. This study verified numerous known VEGF‐A pathway components and revealed several previously unidentified mechanisms of VEGF‐A signaling in BM‐EPCs during hypoxia that may be important for vascular regeneration.