期刊
ANGIOGENESIS
卷 20, 期 1, 页码 85-96出版社
SPRINGER
DOI: 10.1007/s10456-016-9530-9
关键词
Angiogenesis; VEGF; Tissue factor; Factor VII-targeted therapy; Vascular endothelial cells
资金
- CT DPH Biomedical Research Grant [RFP2009-0096]
- Ohio State University College of Medicine
- OSU James Comprehensive Cancer Center (OSUCCC)
- OSUCCC Translational Therapeutics Program
- OSU Center for Clinical and Translational Science through from the National Center For Advancing Translational Sciences [UL1TR001070]
Identification of target molecules specific for angiogenic vascular endothelial cells (VEC), the inner layer of pathological neovasculature, is critical for discovery and development of neovascular-targeting therapy for angiogenesis-dependent human diseases, notably cancer, macular degeneration and endometriosis, in which vascular endothelial growth factor (VEGF) plays a central pathophysiological role. Using VEGF-stimulated vascular endothelial cells (VECs) isolated from microvessels, venous and arterial blood vessels as in vitro angiogenic models and unstimulated VECs as a quiescent VEC model, we examined the expression of tissue factor (TF), a membrane-bound receptor on the angiogenic VEC models compared with quiescent VEC controls. We found that TF is specifically expressed on angiogenic VECs in a time-dependent manner in microvessels, venous and arterial vessels. TF-targeted therapeutic agents, including factor VII (fVII)-IgG1 Fc and fVII-conjugated photosensitizer, can selectively bind angiogenic VECs, but not the quiescent VECs. Moreover, fVII-targeted photodynamic therapy can selectively and completely eradicate angiogenic VECs. We conclude that TF is an angiogenic-specific receptor and the target molecule for fVII-targeted therapeutics. This study supports clinical trials of TF-targeted therapeutics for the treatment of angiogenesis-dependent diseases such as cancer, macular degeneration and endometriosis.
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