期刊
JOURNAL OF VASCULAR RESEARCH
卷 51, 期 2, 页码 110-117出版社
KARGER
DOI: 10.1159/000360085
关键词
Angiogenesis; Vascular endothelial growth factor; Extracellular matrix; Endothelial cells
资金
- American Heart Association Scientist Development [10SDG2570037]
- National Natural Science Foundation of China [81172050]
- Innovation Team of Education Bureau of Sichuan Province [13TD0031]
Background: Vascular endothelial growth factor (VEGF) plays a key role in regulating angiogenesis, and this process is largely dependent on the newly formed extracellular matrix (ECM). The levels of vitronectin (VN) are increased in patients with various cardiovascular diseases. A role for VN in regulating VEGF-induced angiogenesis has not been previously reported. We tested the hypothesis that VN regulates VEGFR-2 activation via effects on alpha(v)beta(3), thus contributing to angiogenesis. Methods: We used a 3-dimensional angiogenesis assay, and examined the effects of VN on VEGF-mediated angiogenesis in aortic endothelial cells (ECs) isolated from wild-type and VN-deficient mice. Results:The addition of multimeric VN significantly enhanced VEGF-induced increases in EC migration and capillaryformation. In vitro, Vn(-/-) ECs migrated significantly slower than wild-type ECs. The addition of VN to Vn(-/-) ECs increased EC migration and augmented the promigratory effect of VEGF in a manner that involved VEGFR-2 and Src signaling. Analysis of the mechanisms involved revealed that multimeric VN, but not monomeric VN, binds VEGF and enhances VEGF-induced VEGFR-2/Src activation in ECs. Conclusion: These results underscore the importance of VN in the regulation of angiogenesis induced by VEGF. (C) 2014 S. Karger AG, Basel
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