Abstract |
Vascular endothelial growth factors ( VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV- VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.
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Authors | Anne Saaristo, Tanja Veikkola, Berndt Enholm, Maija Hytönen, Johanna Arola, Katri Pajusola, Païvi Turunen, Michael Jeltsch, Marika J Karkkainen, Dontscho Kerjaschki, Hansruedi Bueler, Seppo Ylä-Herttuala, Kari Alitalo |
Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology
(FASEB J)
Vol. 16
Issue 9
Pg. 1041-9
(Jul 2002)
ISSN: 1530-6860 [Electronic] United States |
PMID | 12087065
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Angiopoietin-1
- Angpt1 protein, mouse
- Endothelial Growth Factors
- Lymphokines
- Membrane Glycoproteins
- Receptors, Growth Factor
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor C
- Vascular Endothelial Growth Factors
- Receptor Protein-Tyrosine Kinases
- Receptors, Vascular Endothelial Growth Factor
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Topics |
- Adenoviridae
(genetics)
- Angiopoietin-1
- Animals
- Blood Vessels
(anatomy & histology, metabolism)
- Capillary Permeability
(drug effects)
- Cell Line
- Dependovirus
(genetics)
- Endothelial Growth Factors
(genetics, metabolism)
- Genetic Vectors
- Lymphatic System
(growth & development)
- Lymphokines
(genetics)
- Membrane Glycoproteins
(pharmacology)
- Mice
- Mice, Nude
- Nasal Mucosa
(blood supply)
- Neovascularization, Physiologic
- Receptor Protein-Tyrosine Kinases
(metabolism)
- Receptors, Growth Factor
(metabolism)
- Receptors, Vascular Endothelial Growth Factor
- Skin
(blood supply, metabolism)
- Transfection
- Vascular Endothelial Growth Factor A
- Vascular Endothelial Growth Factor C
- Vascular Endothelial Growth Factors
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