@article {27,
	title = {Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function},
	journal = {FASEB J},
	volume = {17},
	year = {2003},
	month = {2003/Nov/},
	pages = {2006 - 13},
	abstract = {Vascular endothelial cells are characterized by a high degree of functional and phenotypic plasticity, which is controlled both by their pericellular microenvironment and their intracellular gene expression programs. To gain further insight into the mechanisms regulating the endothelial cell phenotype, we have compared the responses of lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs) to vascular endothelial growth factors (VEGFs). VEGFR-3-specific signals are sufficient for LEC but not BEC proliferation, as shown by the ability of the specific ligand VEGF-C156S to stimulate cell cycle entry only in LECs. On the other hand, we found that VEGFR-3 stimulation did not induce LEC cell shape changes typical of VEGFR-2-stimulated LECs, indicating receptor-specific differences in the cytoskeletal responses. Genes induced via VEGFR-2 also differed between BECs and LECs: angiopoietin-2 (Ang-2) was induced via VEGFR-2 in BECs and LECs, but the smooth muscle cell (SMC) chemoattractant BMP-2 was induced only in BECs. Both BECs and LECs were able to promote SMC chemotaxis, but contact with SMCs led to down-regulation of VEGFR-3 expression in BECs in a 3-dimensional coculture system. This was consistent with the finding that VEGFR-3 is down-regulated in vivo at sites of endothelial cell-pericyte/smooth muscle cell contacts. Collectively, these data show intrinsic cell-specific differences of BEC and LEC responses to VEGFs and identify a pericellular regulatory mechanism for VEGFR-3 down-regulation in endothelial cells.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/14597670},
	author = {Veikkola, Tanja and Lohela, Marja and Ikenberg, Kristian and M{\"a}kinen, Taija and Korff, Thomas and Saaristo, Anne and Petrova, Tatania and Jeltsch, Michael and Augustin, Hellmut G and Alitalo, Kari}
}
@article {24,
	title = {Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes},
	journal = {FASEB J},
	volume = {16},
	year = {2002},
	month = {2002/Jul/},
	pages = {1041 - 9},
	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.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/12087065},
	author = {Saaristo, Anne and Veikkola, Tanja and Enholm, Berndt and Hyt{\"o}nen, Maija and Arola, Johanna and Pajusola, Katri and Turunen, Pa{\"\i}vi and Jeltsch, Michael and Karkkainen, Marika J and Kerjaschki, Dontscho and Bueler, Hansruedi and Yl{\"a}-Herttuala, Seppo and Alitalo, Kari}
}
